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1.
Blaeser, Andrew S.
Optical Interrogation of the Spontaneous Dynamics of
Prefrontal Cortical Networks.
Degree: PhD, Physics, 2015, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:419386/
► The prefrontal cortex (PFC) is the brain region most strongly associated with many higher cognitive functions such as working memory and decision making. While decades…
(more)
▼ The prefrontal cortex (PFC) is the brain region most
strongly associated with many higher cognitive functions such as
working memory and decision making. While decades of study have
produced a wealth of data about the anatomy and physiology of the
PFC, our knowledge of the mechanisms by which the PFC stores,
represents and processes information is currently incomplete.
Specifically, little is known about the neuronal microcircuits
within the PFC that may represent the basic units underlying its
various functions. A deeper understanding of the network activity
of PFC will likely be critically important for understanding
cognition, and for developing therapies for PFC-related disorders
such as schizophrenia. The advent of functional imaging has enabled
the simultaneous measurement of the activity of large numbers of
neighboring neurons, setting the stage for analysis of cortical
microcircuits on a spatial scale that is inaccessible by
traditional electrophysiological methods. In this thesis, we use
calcium imaging in acute brain slices to characterize the dynamics
of networks within deep-layer medial PFC. Taking advantage of the
brain slice preparation, we use pharmacological agents to
manipulate two molecular systems strongly implicated in network
activity: NMDA receptors and GABAA receptors. We also present a
framework for analyzing the resulting movies. Whereas the majority
of neurons show only sporadic activity, a subset of neurons emit
spontaneous, delta-band rhythmic activity. Looking beyond the
activity of individual neurons, we examine the interactions between
neurons. We find that spontaneous activity under baseline
conditions is weakly correlated between pairs of neurons, and that
rhythmic neurons showed little coherence in their oscillations.
However, we consistently observed brief bouts of synchronous
activity. Using surrogate data sets, we showed that the degree of
correlation and synchrony we observed could not be explained by
coincidence, but must be attributed partly to network activity.
Finally, we described the effects of NMDA and picrotoxin on these
metrics of network dynamics, and discuss possible implications of
these results for understanding the neuronal bases of cognition and
brain diseases.
Advisors/Committee Members: Nurmikko, Arto (Director), Stein, Derek (Reader), Connors, Barry (Reader).
Subjects/Keywords: calcium imaging
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MLA ·
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APA (6th Edition):
Blaeser, A. S. (2015). Optical Interrogation of the Spontaneous Dynamics of
Prefrontal Cortical Networks. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419386/
Chicago Manual of Style (16th Edition):
Blaeser, Andrew S. “Optical Interrogation of the Spontaneous Dynamics of
Prefrontal Cortical Networks.” 2015. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:419386/.
MLA Handbook (7th Edition):
Blaeser, Andrew S. “Optical Interrogation of the Spontaneous Dynamics of
Prefrontal Cortical Networks.” 2015. Web. 16 Jan 2021.
Vancouver:
Blaeser AS. Optical Interrogation of the Spontaneous Dynamics of
Prefrontal Cortical Networks. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:419386/.
Council of Science Editors:
Blaeser AS. Optical Interrogation of the Spontaneous Dynamics of
Prefrontal Cortical Networks. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419386/
2.
Xu, Heng.
Optical Recording and Photo Modulation in the Study of
Dynamics in Neural Circuits.
Degree: PhD, Physics, 2010, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11119/
► Recording and modulation of large neuronal populations are essential for uncovering the dynamical properties of complex neural circuits. In the last few decades, various optical…
(more)
▼ Recording and modulation of large neuronal populations
are essential for uncovering the dynamical properties of complex
neural circuits. In the last few decades, various optical neural
recording and modulation methods have been developed. In this
thesis, I present the synergistic application of three different
optical tools in the study of neural dynamics of two different
neural systems.In the first part, we applied wide field calcium
imaging with a high speed CCD camera to study development of the
visual system of Xenopus laevis tadpoles. Calcium signals from up
to 90 optic tectal neurons were simultaneously recorded with
millisecond temporal resolution. After reconstructing the
electrical neural activity from their calcium signals, we compared
neural synchrony over development, and found that tectal neurons in
older tadpoles responded more synchronously to whole field visual
stimuli when compared to younger animals. To discover the
mechanisms underlying this effect, we reared animals in different
environments during a critical developmental period. Dark-rearing
resulted in a severe disruption in the development of neural
synchrony, indicating that visual experience is crucial for this
process. Blocking NMDA receptors showed a similar but smaller
effect, suggesting that NMDA receptor activation is one mechanism
involved in this process. Experimental results were further
explained using a spike-timing dependent plasticity-based neural
network model. Moreover, using a specially fabricated
matrix-addressable LED array-based image projection device to
generate visual stimuli, we found that tectal neurons of older
animals showed much sharper and more refined visual receptive
fields.In the second part, we genetically targeted and expressed a
photosensitive cation channel channelrhodopsin-2 on mouse medial
dorsal nucleus (MDN) of the thalamus to study how the MDN axon
inputs affect the collective activity of prefrontal cortical
neurons. Photostimulation of channelrhodopsin-2 expressing MDN
axons in mouse prefrontal cortical slices triggered spiking
activity with millisecond temporal precision, which allows MDN-axon
specific optical activation. Combined with calcium imaging, we
found that MDN inputs can elicit synchronous activity in PFC, which
is believed to play an essential role in working memory. This
suggests that MDN may also be involved in working
memory.
Advisors/Committee Members: Nurmikko, Arto (Director), Connors, Barry (Reader), Valles, James (Reader).
Subjects/Keywords: LED array
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Xu, H. (2010). Optical Recording and Photo Modulation in the Study of
Dynamics in Neural Circuits. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11119/
Chicago Manual of Style (16th Edition):
Xu, Heng. “Optical Recording and Photo Modulation in the Study of
Dynamics in Neural Circuits.” 2010. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:11119/.
MLA Handbook (7th Edition):
Xu, Heng. “Optical Recording and Photo Modulation in the Study of
Dynamics in Neural Circuits.” 2010. Web. 16 Jan 2021.
Vancouver:
Xu H. Optical Recording and Photo Modulation in the Study of
Dynamics in Neural Circuits. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:11119/.
Council of Science Editors:
Xu H. Optical Recording and Photo Modulation in the Study of
Dynamics in Neural Circuits. [Doctoral Dissertation]. Brown University; 2010. Available from: https://repository.library.brown.edu/studio/item/bdr:11119/
3.
Zhang, Jiayi.
Optical Stimulation and Spatiotemporal Electrical Recording
ni Genetically Targeted Brain Tissue.
Degree: PhD, Physics, 2009, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:201/
► Neural stimulation with spatial and temporal precision is desirable both for studying the real-time dynamics of neural networks, and for prospective clinical treatment of neurological…
(more)
▼ Neural stimulation with spatial and temporal precision
is desirable both for studying the real-time dynamics of neural
networks, and for prospective clinical treatment of neurological
diseases. Optical stimulation of genetically targeted neurons
expressing the light sensitive channel Channelrhodopsin (ChR2) has
recently been reported as a method for millisecond temporal control
of neuronal spiking activities with cell-type selectivity. In this
thesis, I present a novel dual-modality device which consists of a
tapered coaxial optical waveguide "optrode" integrated into a 100
element multi-electrode microscale intracortical recording array.
The structure was designed by considering general guided wave
electromagnetic principles for the "optrode" on one hand, and the
photon diffusion/scattering in the brain tissue from a micron-size
shaped aperture, on the other. The dual optical delivery and
electrical recording capability of the optrode was first
demonstrated and validated in in vitro preparations of mouse
retina, photostimulating the native retinal photoreceptors while
recording light-responsive activities from ganglion cells. The
dual-modality device was then used in ChR2 transfected mouse brain
slices. Specifically, epileptiform events are reliably optically
triggered by the optrode, and their spatiotemporal patterns are
simultaneously recorded through the multi-electrode array, and
shown to be consistent with models for epileptiform wave-like
propagation.
Advisors/Committee Members: Nurmikko, Arto (director), Connors, Barry (director), Valles, James (reader).
Subjects/Keywords: optogenetics; channelrhodopsin(ChR2); optrode; microelectrode
array; neural stimulation; retinal recording
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, J. (2009). Optical Stimulation and Spatiotemporal Electrical Recording
ni Genetically Targeted Brain Tissue. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:201/
Chicago Manual of Style (16th Edition):
Zhang, Jiayi. “Optical Stimulation and Spatiotemporal Electrical Recording
ni Genetically Targeted Brain Tissue.” 2009. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:201/.
MLA Handbook (7th Edition):
Zhang, Jiayi. “Optical Stimulation and Spatiotemporal Electrical Recording
ni Genetically Targeted Brain Tissue.” 2009. Web. 16 Jan 2021.
Vancouver:
Zhang J. Optical Stimulation and Spatiotemporal Electrical Recording
ni Genetically Targeted Brain Tissue. [Internet] [Doctoral dissertation]. Brown University; 2009. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:201/.
Council of Science Editors:
Zhang J. Optical Stimulation and Spatiotemporal Electrical Recording
ni Genetically Targeted Brain Tissue. [Doctoral Dissertation]. Brown University; 2009. Available from: https://repository.library.brown.edu/studio/item/bdr:201/
4.
Kim, Jennifer A.
Febrile Seizures, Hyperthermia and Hippocampal Neuron
Physiology.
Degree: PhD, Neuroscience, 2010, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11064/
► Temperature is a fundamental property that affects all biologic systems, including the brain. The high temperatures of fever states can trigger febrile seizures in children,…
(more)
▼ Temperature is a fundamental property that affects all
biologic systems, including the brain. The high temperatures of
fever states can trigger febrile seizures in children, yet little
is known about the effects of hyperthermic temperatures on the
excitability of the immature nervous system. Febrile seizures cause
long-term cellular and molecular changes in the hippocampus.
However, acute effects of hyperthermia on hippocampal neurons have
not been studied. My project was motivated by the need to
understand the effects of hyperthermia and the mechanisms of
febrile seizures. I studied the effects of hyperthermic
temperatures on the physiology of neurons, synapses, and circuits
in the juvenile mouse hippocampus. My central hypothesis is that
febrile seizures arise from substantial hyperthermia-induced
excitation. I found that hyperthermia increased the excitability of
all principal cells in the hippocampus. However CA3 pyramidal cells
were significantly more responsive than either CA1 pyramidal cells
or the granule cells of the dentate gyrus (Chapter 2). Changes in
synaptic inhibition are common causes of seizure generation. I
examined the effects of hyperthermia on a major class of
hippocampal inhibitory cell, the O-LM interneurons (identified by
their green fluorescent protein expression in a transgenic mouse
line). O-LM interneurons were strongly excited by heat, and CA3
O-LM cells were more responsive than those in CA1 (Chapter 3).
Although all proteins are affected by temperature, some
types – including the heat-activated TRPV1 channels – are
particularly sensitive and may play an important role in brain
function (Gibson et al., 2008). I tested whether TRPV1 channels
influence febrile seizure susceptibility. The absence of TRPV1
channels increased the temperature threshold for behavioral
hyperthermic seizures and reduced heat-activated multiunit activity
in hippocampus in vitro (Chapter 4). My results demonstrate that
hyperthermic temperatures increase the excitability of all major
classes of hippocampal neurons, and suggest that heat-sensitive
TRPV1 channels may modulate the threshold for febrile
seizures.
Advisors/Committee Members: Connors, Barry (Director), Berson, David (Reader), Kauer, Julie (Reader), Zimmerman, Anita (Reader), Blumenfeld, Hal (Reader).
Subjects/Keywords: febrile seizures
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kim, J. A. (2010). Febrile Seizures, Hyperthermia and Hippocampal Neuron
Physiology. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11064/
Chicago Manual of Style (16th Edition):
Kim, Jennifer A. “Febrile Seizures, Hyperthermia and Hippocampal Neuron
Physiology.” 2010. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:11064/.
MLA Handbook (7th Edition):
Kim, Jennifer A. “Febrile Seizures, Hyperthermia and Hippocampal Neuron
Physiology.” 2010. Web. 16 Jan 2021.
Vancouver:
Kim JA. Febrile Seizures, Hyperthermia and Hippocampal Neuron
Physiology. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:11064/.
Council of Science Editors:
Kim JA. Febrile Seizures, Hyperthermia and Hippocampal Neuron
Physiology. [Doctoral Dissertation]. Brown University; 2010. Available from: https://repository.library.brown.edu/studio/item/bdr:11064/
5.
Neske, Garrett T.
Roles of diverse inhibitory interneurons and mechanisms of
synchronized inhibition in active cortical networks.
Degree: PhD, Neuroscience, 2016, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:674130/
► The neocortex contains two categories of neurons: excitatory neurons, which enhance other neurons’ activities, and inhibitory interneurons, which decrease other neurons’ activities. Balanced activation of…
(more)
▼ The neocortex contains two categories of neurons:
excitatory neurons, which enhance other neurons’ activities, and
inhibitory interneurons, which decrease other neurons’ activities.
Balanced activation of these two cell types is essential to proper
cortical function. Interneuron subtypes are diverse, but their
distinct circuit-level roles are not well understood. My goal was
to study the contributions of diverse interneuron subtypes during
spontaneous activity in the local cortical network. These periods
of activity (Up states) occur during the local network oscillations
of quiescent behavior, such as slow-wave sleep. Spontaneous Up
states also occur in isolated cortical slices. I recorded from
individual excitatory cells and diverse inhibitory interneurons
during Up states in slices of mouse somatosensory cortex in vitro.
In part one, I showed that multiple interneuron subtypes exhibit
robust spiking during Up states. While fast-spiking PV cells were
the most active, other interneuron subtypes were as active or more
active than excitatory cells. Interestingly, the situation was
quite different in another cortical region, the entorhinal cortex:
PV cells were virtually the only active interneuron subtype. This
suggests that the contribution of interneuron subtypes to Up states
may vary among cortical regions. In part two, I further studied the
contributions of two interneuron subtypes: SOM cells and VIP cells.
I showed that while optogenetic silencing of SOM cells removed a
functionally significant amount of inhibition from excitatory cells
during Up states, silencing VIP cells did not have an effect on
excitatory cells. Furthermore, despite the inhibition of SOM cells
by VIP cells, optogenetic activation of VIP cells also did not
affect the activity of excitatory cells. These results suggest that
the contribution of VIP cells during network activity may depend on
cortical state. In part three, I studied the mechanisms of
interneuron spike synchrony during Up states. I showed that
interneurons exhibit precise spike synchrony, which is largely
insensitive to the absence of electrical synapses. I also presented
evidence that the most likely mechanism of spike synchrony is
shared excitatory drive. The results of this thesis provide new
insight about the contributions of diverse interneuron subtypes in
the active cortex.
Advisors/Committee Members: Connors, Barry (Director), Berson, David (Reader), Truccolo, Wilson (Reader), Cardin, Jessica (Reader).
Subjects/Keywords: cortex
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Neske, G. T. (2016). Roles of diverse inhibitory interneurons and mechanisms of
synchronized inhibition in active cortical networks. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:674130/
Chicago Manual of Style (16th Edition):
Neske, Garrett T. “Roles of diverse inhibitory interneurons and mechanisms of
synchronized inhibition in active cortical networks.” 2016. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:674130/.
MLA Handbook (7th Edition):
Neske, Garrett T. “Roles of diverse inhibitory interneurons and mechanisms of
synchronized inhibition in active cortical networks.” 2016. Web. 16 Jan 2021.
Vancouver:
Neske GT. Roles of diverse inhibitory interneurons and mechanisms of
synchronized inhibition in active cortical networks. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:674130/.
Council of Science Editors:
Neske GT. Roles of diverse inhibitory interneurons and mechanisms of
synchronized inhibition in active cortical networks. [Doctoral Dissertation]. Brown University; 2016. Available from: https://repository.library.brown.edu/studio/item/bdr:674130/
6.
Ahmed, Omar Jamil.
Interpreting the Rhythms of the Hippocampus and
Neocortex.
Degree: PhD, Neuroscience, 2010, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11044/
► When groups of neurons are synchronously and rhythmically active, they give rise to electrical oscillations that can be seen in the surrounding extracellular local field…
(more)
▼ When groups of neurons are synchronously and
rhythmically active, they give rise to electrical oscillations that
can be seen in the surrounding extracellular local field potential
(LFP) and in scalp electroencephalography (EEG) recordings. The
frequencies of these oscillations range from slow (0.3-4 Hz) delta
oscillations during sleep to very fast (300 Hz) ripple oscillations
during epileptic seizures. The appearance of intermediate gamma
frequency oscillations (40-80 Hz) is associated with active sensory
processing, increased attention and improved reaction times. Gamma
rhythms are often altered in patients diagnosed with schizophrenia,
bipolar disorder, depression, ADHD, tinnitus and epilepsy,
suggesting that a deeper understanding of the gamma signal may help
to elucidate the differences between normal and pathological neural
circuits.Using tetrode recordings from the hippocampus and
neocortex of freely behaving rats, this thesis examines both the
behavioral and mechanistic underpinnings of gamma oscillations. We
show that increased running speed is accompanied by large,
systematic increases in the frequency of hippocampal CA1 network
oscillations spanning the entire gamma range and beyond. These
speed-dependent changes are seen on both linear tracks and
two-dimensional platforms, and are thus independent of spatial
environment. We hypothesize that the faster gamma oscillations may
be indicative of faster reaction times and improved perception at
faster running speeds.Individual gamma cycles are less than 20 ms
in duration and show large, cycle-by-cycle changes in amplitude and
frequency. We also show that these rapid LFP changes are
accompanied by instantaneous, cycle-by-cycle changes in
spike-timing precision of cells in the neocortex. The slope of an
individual LFP gamma cycle encodes the amount of spike synchrony
during that gamma cycle, but provides no information about
synchrony in the very next cycle. These changes in spike synchrony
are preceded by corresponding changes in spike rate in the previous
gamma cycle. Thus, local cortical circuits transform asynchronous
increases in spike rate into fewer, but more synchronous spikes
within a single gamma cycle. This sequence can be reliably
predicted by the slope of individual gamma cycles, with important
implications for the design of brain-machine
interfaces.
Advisors/Committee Members: Connors, Barry (Director), Mehta, Mayank (Director), Lipscombe, Diane (Reader), Burwell, Rebecca (Reader), Knierim, James (Reader).
Subjects/Keywords: gamma
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ahmed, O. J. (2010). Interpreting the Rhythms of the Hippocampus and
Neocortex. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11044/
Chicago Manual of Style (16th Edition):
Ahmed, Omar Jamil. “Interpreting the Rhythms of the Hippocampus and
Neocortex.” 2010. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:11044/.
MLA Handbook (7th Edition):
Ahmed, Omar Jamil. “Interpreting the Rhythms of the Hippocampus and
Neocortex.” 2010. Web. 16 Jan 2021.
Vancouver:
Ahmed OJ. Interpreting the Rhythms of the Hippocampus and
Neocortex. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:11044/.
Council of Science Editors:
Ahmed OJ. Interpreting the Rhythms of the Hippocampus and
Neocortex. [Doctoral Dissertation]. Brown University; 2010. Available from: https://repository.library.brown.edu/studio/item/bdr:11044/
7.
Urabe, Hayato.
Optical Elucidation of Neural Microcircuitry.
Degree: PhD, Biomedical Engineering, 2009, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:216/
► The neural networks consisting of the axonal tracts that interconnect the thalamus and the neocortex are central to information processing where the thalamus acts as…
(more)
▼ The neural networks consisting of the axonal tracts
that interconnect the thalamus and the neocortex are central to
information processing where the thalamus acts as the ?gateway' to
the neocortex where almost all sensory information passes. Research
on TC projection has been relying on electrical stimulation in
brain slices, where it has been a big challenge to contain all the
projections in a thin slab of tissue. Channelrhodopsin-2 (ChR2), a
light-sensitive cation-channel derived from green algae,
chlamydomonas reinhardtii, was used as a potential alternative for
electrical stimulation. Lentivirus coding for ChR2 was
intracranially injected into mice to render neurons
photo-sensitive. With the ability to genetically target the
expression of ChR2 to neurons using synapsin-I promoter and using
lentiviral construct without retrograde infection, successful
expression of ChR2 along the TC axonal tract was achieved. Taking
advantage of ChR2's ability to spatiotemporally control the
activity of neurons by the illumination of pulses of blue light
(wavelength ~440nm), we have successfully activated the neurons
both directly and synaptically. Synaptic activation allowed light
activation of neurons that did not express ChR2 on the cell
membrane. Furthermore, activation of brain-region remote from the
injection site (thalamus) and close to the surface of the brain
(cortex) was possible, taking advantage of the anatomical features
of the projection neurons The results of synaptic activation of the
axonal terminus in slice studies were extended to in vivo scenario
using engineered single-unit optical electrode (SUOE) as the
optical activation-electrical recording modality. Optically-evoked
temporary-precise multi-unit activities were observed in the cortex
upon light illumination of the TC axonal terminals. Kubelka-Munk
model was used to calculate the minimum light intensity that was
required to elicit response from the TC axonal terminals.
Exploration of potential non-viral gene transfer of ChR2 was also
attempted. Using silica nanoparticles, successful gene delivry of
ChR2-coding DNA into cortical cells of live mouse brain was
achieved. Light-evoked modulation of transfected neural cells was
confirmed using standard electrophysiology and semi-quantitative
comparison with viral infection was conducted.
Advisors/Committee Members: Nurmikko, Arto (director), Connors, Barry (reader), Palmore, G.Tayhas (reader), Hurt, Robert (reader), Rasmussen, Steven (reader).
Subjects/Keywords: Optogenetics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Urabe, H. (2009). Optical Elucidation of Neural Microcircuitry. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:216/
Chicago Manual of Style (16th Edition):
Urabe, Hayato. “Optical Elucidation of Neural Microcircuitry.” 2009. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:216/.
MLA Handbook (7th Edition):
Urabe, Hayato. “Optical Elucidation of Neural Microcircuitry.” 2009. Web. 16 Jan 2021.
Vancouver:
Urabe H. Optical Elucidation of Neural Microcircuitry. [Internet] [Doctoral dissertation]. Brown University; 2009. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:216/.
Council of Science Editors:
Urabe H. Optical Elucidation of Neural Microcircuitry. [Doctoral Dissertation]. Brown University; 2009. Available from: https://repository.library.brown.edu/studio/item/bdr:216/
8.
Normand, Elizabeth A.
Genetic disruption of the thalamus in the context of the
neurodevelopmental disorder Tuberous Sclerosis.
Degree: PhD, Neuroscience, 2013, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:320574/
► The primary objective of this thesis is to investigate the consequences of TSC1 gene deletion in a subcortical brain structure, the thalamus, during embryonic development.…
(more)
▼ The primary objective of this thesis is to investigate
the consequences of TSC1 gene deletion in a subcortical brain
structure, the thalamus, during embryonic development. Mutations in
the TSC1 gene cause Tuberous Sclerosis, a developmental disorder
with significant neurological symptoms including epilepsy, autism,
and intellectual disability. At the cellular level, TSC1 gene
deletion leads to loss of inhibition on the mTOR pathway. The mTOR
pathway is a signaling hub that controls a wide variety of cellular
processes, suggesting that differential phenotypes may result from
TSC1 gene deletion depending on the developmental and regional
context in which the TSC1 mutation occurs. Much of the research
into TSC1 loss of function has focused on the cerebral cortex thus
far. However, clinical MRI imaging studies have implicated
subcortical structures such as the thalamus as playing a role in
cognitive disabilities of patients with Tuberous Sclerosis.
In this thesis, I experimentally tested the role of Tsc1 in
the development of this subcortical structure in mice. I first
characterized the normal development of axonal projection patterns
within a particular lineage of thalamic precursors, Gbx2-expressing
cells, using genetic inducible fate mapping and conditional genetic
circuit tracing. In subsequent experiments, I then applied this
combination of cell marking and circuit analysis to characterize
mutant mice in which the Tsc1 gene had been deleted specifically
within Gbx2-expressing thalamic neurons. By comparing and
contrasting the phenotypes that arose from Tsc1 deletion at two
distinct embryonic stages, I attained insight into the distinct
requirements for Tsc1 function in the thalamus in these two
developmental contexts. Deletion of thalamic Tsc1 at an early
embryonic stage led to excessive cell growth, aberrant protein
expression, axonal disorganization, altered neural activity,
seizures and repetitive grooming behaviors. Deletion at an later
stage produced only a subset of these phenotypes. In addition to
differences in developmental timing, the number and distribution of
mutant cells at these two stages also differed. This complex
interplay of developmental timing and degree of mosaicism is
discussed in the context of the mosaic nature of Tuberous
Sclerosis.
Advisors/Committee Members: Zervas, Mark (Director), Fallon, Justin (Reader), Connors, Barry (Reader), Barnea, Gilad (Reader), Kwiatkowski, David (Reader).
Subjects/Keywords: Tsc1
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Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Normand, E. A. (2013). Genetic disruption of the thalamus in the context of the
neurodevelopmental disorder Tuberous Sclerosis. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:320574/
Chicago Manual of Style (16th Edition):
Normand, Elizabeth A. “Genetic disruption of the thalamus in the context of the
neurodevelopmental disorder Tuberous Sclerosis.” 2013. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:320574/.
MLA Handbook (7th Edition):
Normand, Elizabeth A. “Genetic disruption of the thalamus in the context of the
neurodevelopmental disorder Tuberous Sclerosis.” 2013. Web. 16 Jan 2021.
Vancouver:
Normand EA. Genetic disruption of the thalamus in the context of the
neurodevelopmental disorder Tuberous Sclerosis. [Internet] [Doctoral dissertation]. Brown University; 2013. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:320574/.
Council of Science Editors:
Normand EA. Genetic disruption of the thalamus in the context of the
neurodevelopmental disorder Tuberous Sclerosis. [Doctoral Dissertation]. Brown University; 2013. Available from: https://repository.library.brown.edu/studio/item/bdr:320574/
9.
Graham, Dustin M.
Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in
the Mammalian Eye.
Degree: PhD, Neuroscience, 2009, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:94/
► Melanopsin ganglion cells are a new class of mammalian photoreceptor involved in non-image forming visual reflexes including photoentrainment of circadian rhythms and the pupillary light…
(more)
▼ Melanopsin ganglion cells are a new class of mammalian
photoreceptor involved in non-image forming visual reflexes
including photoentrainment of circadian rhythms and the pupillary
light reflex. Recent evidence has suggested that these cells may
transduce light using a mechanism similar to invertebrate
rhabdomeric photoreceptors, making them unique among all known
vertebrate retinal photoreceptor cell types. However, direct
evidence into the molecular mechanisms of melanopsin ganglion cell
phototransduction has been difficult to acquire due to technical
difficulties. Most problematic has been the lack of methodology to
isolate healthy, photosensitive melanopsin cells for patch-clamp
electrophysiology, pharmacology, and molecular studies. This thesis
presents original work in the design and development of methods to
identify, isolate, and study melanopsin ganglion cells under
conditions sufficient for a thorough investigation of the
phototransduction cascade. This work also presents the first direct
evidence that melanopsin ganglion cells use an invertebrate-like
rhabdomeric mechanism for transducing light, adding further weight
to the hypothesis that these cells are the evolutionary descendants
of rhabdomeric ancestors and that all animals eyes have a common
origin.
Advisors/Committee Members: Berson, David (director), connors, barry (reader), zimmerman, anita (reader), hattar, samer (reader).
Subjects/Keywords: melanopsin phototransduction
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Graham, D. M. (2009). Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in
the Mammalian Eye. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:94/
Chicago Manual of Style (16th Edition):
Graham, Dustin M. “Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in
the Mammalian Eye.” 2009. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:94/.
MLA Handbook (7th Edition):
Graham, Dustin M. “Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in
the Mammalian Eye.” 2009. Web. 16 Jan 2021.
Vancouver:
Graham DM. Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in
the Mammalian Eye. [Internet] [Doctoral dissertation]. Brown University; 2009. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:94/.
Council of Science Editors:
Graham DM. Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in
the Mammalian Eye. [Doctoral Dissertation]. Brown University; 2009. Available from: https://repository.library.brown.edu/studio/item/bdr:94/
10.
Hynes, Jacqueline Bernadette.
Network Interactions during Contextual Information
Processing in Macaque Primary Visual Cortex.
Degree: PhD, Neuroscience, 2016, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:674342/
► The important task of the visual system is to extract and organize meaningful image information in a way that is useful for an organism for…
(more)
▼ The important task of the visual system is to extract
and organize meaningful image information in a way that is useful
for an organism for interacting with its environment. Integral to
the meaningful organization of visual information are contextual
interactions. Contextual interactions refer to phenomena for which
information perceived at one point of visual space is influenced by
information in the surrounding regions. One's ability to perceive
even the most basic attributes of objects depend on such
interactions. Contextual information processing likely relies on
the integration of information from millions of neurons across
multiple cortical regions. Much of what is known about visual
information processing has come from the study of single neuron
behavior, however. As a result, very little is known about the
circuitry underlying contextual information processing. Here, the
spatial integration properties of visual neurons were examined
using V1 multi-electrode array recordings during surround
suppression. Surround suppression refers to the phenomena in which
a cell’s response to a stimulus located inside its classical
receptive field (crf) is suppressed by stimuli located outside its
crf. This thesis focuses on two important questions: 1) what
circuits mediate the suppressive effect of the surround, and 2)
what role do inhibitory networks play in mediating suppression. To
answer question 1, the propagation speed of the surround signal was
estimated to determine if slowly conducting horizontal connections
could account for the speed of suppression onset or if fast
feedback connections might be involved. To answer question 2, the
behavior of putative fast-spiking inhibitory (FS) cells and local
field potentials (LFP) signatures of inhibitory network activity
were examined during suppression. Finally, a characterization of
the spatiotemporal dynamics of network interactions was carried out
during surround suppression through an analysis of LFP-LFP
coherence. Results show that surround suppression likely consists
of multiple components, the earliest of which is faster than can be
explained by horizontal connections. Additionally, FS cell activity
decreased during surround suppression while LFP signatures of
inhibitory network activity increased suggesting that V1 networks
could function in an inhibition stabilized regime during
center-surround interactions.
Advisors/Committee Members: Paradiso, Michael (Director), Connors , Barry (Reader), Serre, Thomas (Reader), Born, Richard (Reader).
Subjects/Keywords: context
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hynes, J. B. (2016). Network Interactions during Contextual Information
Processing in Macaque Primary Visual Cortex. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:674342/
Chicago Manual of Style (16th Edition):
Hynes, Jacqueline Bernadette. “Network Interactions during Contextual Information
Processing in Macaque Primary Visual Cortex.” 2016. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:674342/.
MLA Handbook (7th Edition):
Hynes, Jacqueline Bernadette. “Network Interactions during Contextual Information
Processing in Macaque Primary Visual Cortex.” 2016. Web. 16 Jan 2021.
Vancouver:
Hynes JB. Network Interactions during Contextual Information
Processing in Macaque Primary Visual Cortex. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:674342/.
Council of Science Editors:
Hynes JB. Network Interactions during Contextual Information
Processing in Macaque Primary Visual Cortex. [Doctoral Dissertation]. Brown University; 2016. Available from: https://repository.library.brown.edu/studio/item/bdr:674342/
11.
Fogerson, Patricia M.
Output streams of intrinsically photosensitive ganglion
cells: Distinct types supply different visual and limbic
networks.
Degree: PhD, Neuroscience, 2015, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:419492/
► Retinal ganglion cells (RGCs) transmit visual information encoded by the retina to over 20 different subcortical brain areas. Many of these brain regions receive input…
(more)
▼ Retinal ganglion cells (RGCs) transmit visual
information encoded by the retina to over 20 different subcortical
brain areas. Many of these brain regions receive input from
multiple classes of RGCs, each of which convey a different visual
feature. RGCs with similar physiological properties project to
subregions within subcortical targets; this anatomical
specialization partially determines the relevant features for
visual behavior. Intrinsically photosensitive RGCs (ipRGCs) express
the photopigment melanopsin and can transduce light independently
from the rest of the retina. Of the 6 documented ipRGC subtypes, M1
ipRGCs most faithfully encode ambient light level. Instead of
contributing to thalamic pathways for image perception, M1 ipRGC
axons target hypothalamic and pretectal centers that drive
reflexive visual behaviors. M1 ipRGC axons form a shell around the
outside of the olivary pretectal nucleus (OPN), while other RGC
types densely innervate its central core. Chapter 2 asks whether
the OPN core and shell might direct distinct visual behaviors. Cre
lines are used to selectively target subsets of OPN shell or core
neurons and compare their connectivity and intrinsic physiology.
Results describe two output pathways to neighboring subregions of
visual thalamus from physiologically distinct shell and core
neurons. Furthermore, cre-dependent monosynaptic retrograde tracing
reveals a circuit linking On-alpha RGCs to visual association
thalamus through the OPN shell. Thus, the OPN houses multiple
channels that contribute to both cortical vision and visual
reflexes. Melanopsin phototransduction has also been linked to
light-induced changes in sleep, pain, and mood that are independent
from circadian behavior. No neural circuit has been proposed that
directly links ipRGCs to limbic networks that govern mood. Chapter
3 examines an M1 terminal field at the thalamus-epithalamus border
in the context of limbic circuitry. Results show that this
parahabenular thalamic zone (PHb) is anatomically distinct from
neighboring thalamic and epithalamic structures in terms of both
molecular markers and connectivity, receiving both limbic and
visual afferents. Most notably, the PHb houses neurons that project
to infralimbic cortex, a major node in limbic networks involved in
depression. The PHb is poised to relay ambient light information
encoded by M1 ipRGCs to influence emotional processing in
infralimbic cortex.
Advisors/Committee Members: Berson, David (Director), Connors, Barry (Reader), Sheinberg, David (Reader), Do, Michael (Reader).
Subjects/Keywords: melanopsin
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fogerson, P. M. (2015). Output streams of intrinsically photosensitive ganglion
cells: Distinct types supply different visual and limbic
networks. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419492/
Chicago Manual of Style (16th Edition):
Fogerson, Patricia M. “Output streams of intrinsically photosensitive ganglion
cells: Distinct types supply different visual and limbic
networks.” 2015. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:419492/.
MLA Handbook (7th Edition):
Fogerson, Patricia M. “Output streams of intrinsically photosensitive ganglion
cells: Distinct types supply different visual and limbic
networks.” 2015. Web. 16 Jan 2021.
Vancouver:
Fogerson PM. Output streams of intrinsically photosensitive ganglion
cells: Distinct types supply different visual and limbic
networks. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:419492/.
Council of Science Editors:
Fogerson PM. Output streams of intrinsically photosensitive ganglion
cells: Distinct types supply different visual and limbic
networks. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419492/
12.
Dobson, Lauren G.
Loss of connexin36-mediated gap junctions impairs odor
discrimination in mice.
Degree: PhD, Neuroscience, 2016, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:674201/
► In the mammalian central nervous system, gap junctions made up of connexin36 are the basis of electrical communication between many neurons. Interneurons throughout the neocortex,…
(more)
▼ In the mammalian central nervous system, gap junctions
made up of connexin36 are the basis of electrical communication
between many neurons. Interneurons throughout the neocortex,
hippocampus, and amygdala; inferior olivary neurons; various types
of retinal neurons; and mitral cells of the olfactory bulb are all
known to be coupled by connexin36, with no other connexin protein
able to compensate and form alternative gap junctions when
connexin36 is absent. Much research has been done to characterize
the electrophysiological and structural consequences of connexin36
deletion, but behavior has been studied sparsely and with some
conflicting results. Given its widespread expression and the
apparent dearth of direct compensation mechanisms in its absence,
examining the performance of connexin36 knockout mice during a wide
range of behavioral tasks might provide us with more information
about the role of synchrony within neuronal populations. In this
thesis, I strive to clarify previously-described behavioral results
and characterize more thoroughly the behavioral effects of
connexin36 knockout. Through three batteries of tasks designed to
test sensorimotor, cognitive, and affective behaviors, we revealed
that connexin36 knockout and heterozygous animals are more active
and less anxious than wild-type littermates, display differing
aberrant contextual fear responses, and perform poorly on an
olfactory recognition task. Taking a closer look at olfactory
behavior in particular, I uncovered an odor discrimination deficit
in connexin36 knockout mice. Finally, I began to generate a
conditional knockout mouse line to delete connexin36 only in mitral
cells of the olfactory bulb, which will allow me to examine the
olfactory deficit in more detail.
Advisors/Committee Members: Barnea, Gilad (Director), Burwell, Rebecca (Reader), Connors, Barry (Reader), Davison, Ian (Reader).
Subjects/Keywords: Gap junctions
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dobson, L. G. (2016). Loss of connexin36-mediated gap junctions impairs odor
discrimination in mice. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:674201/
Chicago Manual of Style (16th Edition):
Dobson, Lauren G. “Loss of connexin36-mediated gap junctions impairs odor
discrimination in mice.” 2016. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:674201/.
MLA Handbook (7th Edition):
Dobson, Lauren G. “Loss of connexin36-mediated gap junctions impairs odor
discrimination in mice.” 2016. Web. 16 Jan 2021.
Vancouver:
Dobson LG. Loss of connexin36-mediated gap junctions impairs odor
discrimination in mice. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:674201/.
Council of Science Editors:
Dobson LG. Loss of connexin36-mediated gap junctions impairs odor
discrimination in mice. [Doctoral Dissertation]. Brown University; 2016. Available from: https://repository.library.brown.edu/studio/item/bdr:674201/
13.
Lee, Seung-Chan.
Development, organization and function of electrical
synapses in the thalamus.
Degree: PhD, Neuroscience, 2010, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11096/
► The thalamus is an important subcortical structure that relays afferent information to the neocortex, provides a pathway for corticocortical interaction, and plays key roles in…
(more)
▼ The thalamus is an important subcortical structure
that relays afferent information to the neocortex, provides a
pathway for corticocortical interaction, and plays key roles in
thalamocortical rhythm generation. My thesis addressed three main
questions related to the characteristics and functions of
electrical synapses in the thalamus. First, I examined electrical
synapses between thalamic relay neurons in the ventrobasal complex
(VB). I found that electrical coupling between VB neurons was
common during the first postnatal week, but was rapidly eliminated
as intrathalamic chemical synaptic pathways matured during the
first and second postnatal weeks. This suggests a transient
developmental role for VB coupling. Second, I characterized the
spatial structure of gap junction-coupled networks of GABAergic
neurons in the thalamic reticular nucleus (TRN) using a novel
dye-coupling technique. The number of coupled neurons per cluster
varied from 2 to 23, with an average of 8 neurons. Intersomatic
distances between coupled neurons ranged from 10-340 micrometer and
averaged about 100 micrometer. The majority of cell clusters were
rod- and disc-shaped, with their major axis parallel to the VB/TRN
border plane and a narrow spread along the short axis of the TRN. A
minor population of TRN neurons formed spherical patterns in which
coupled neurons spread along all three main axes. Rod- and
disc-like clusters were most likely to connect functionally similar
TRN neurons targeting neighboring relay neurons, whereas
sphere-like clusters spread across different TRN tiers that could
integrate activity from functionally distinct TRN neurons. Third, I
addressed the role of electrical coupling between TRN neurons by
measuring the synchrony of inhibitory synaptic events in VB relay
neurons from wild-type and Cx36 knockout mice recorded in vitro.
The strength of inhibitory synchrony varied widely and tended to
depend on intercellular distance, but the synchrony among VB
neurons of different genotypes was not significantly different.
These results suggest possible contributions of both common axonal
inputs and electrical synapses to inhibitory synchrony between
relay neurons. Overall, my research implies that electrical
synapses are an important feature of thalamic circuitry that
depends on maturation, spatial organization, and local network
function.
Advisors/Committee Members: Connors, Barry (Director), Berson, David (Reader), Kauer, Julie (Reader), Deschenes, Martin (Reader).
Subjects/Keywords: electrical synapses
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, S. (2010). Development, organization and function of electrical
synapses in the thalamus. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11096/
Chicago Manual of Style (16th Edition):
Lee, Seung-Chan. “Development, organization and function of electrical
synapses in the thalamus.” 2010. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:11096/.
MLA Handbook (7th Edition):
Lee, Seung-Chan. “Development, organization and function of electrical
synapses in the thalamus.” 2010. Web. 16 Jan 2021.
Vancouver:
Lee S. Development, organization and function of electrical
synapses in the thalamus. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:11096/.
Council of Science Editors:
Lee S. Development, organization and function of electrical
synapses in the thalamus. [Doctoral Dissertation]. Brown University; 2010. Available from: https://repository.library.brown.edu/studio/item/bdr:11096/
14.
Hayes, Lindsay Nicole.
Temporal Control of Sonic Hedgehog Signaling for Midbrain
Dopamine Neuron Development.
Degree: PhD, Neuroscience, 2012, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:297700/
► The aim of this thesis research is to elucidate the genetic regulatory mechanisms that link the primordial neural ectoderm to the diverse array of neurons…
(more)
▼ The aim of this thesis research is to elucidate the
genetic regulatory mechanisms that link the primordial neural
ectoderm to the diverse array of neurons that comprise the complex
adult nervous system. I focused on midbrain dopamine (mDA) neurons
which originate from the ventral mesencephalon (vMes) and are
partitioned into anatomically distinct functional domains,
including the substantia nigra pars compacta (SNc) and ventral
tegmental area (VTA). Among many genes that govern the regional
patterning and cell fate specification, Sonic hedgehog (Shh) is
important for tissue patterning, proliferation, and cell fate
specification in the vMes; notably Shh signaling induces Gli1
expression in Shh-responding cells. To further investigate the
developmental genetic mechanisms that regulate the diversity of mDA
neurons, I employed genetic inducible fate mapping and conditional
loss- and gain-of-function approaches in mice. I demonstrated that
Shh and Gli1 genetic lineages cumulatively contribute to
overlapping mDA neuron subtypes, and the timing of each lineage's
contribution to the SNc and VTA was distinct. I carefully dissected
the temporal relationship between the Shh and Gli1 expressing cells
during vMes development. I discovered that all Shh expressing cells
were derived from progenitors that had previously responded to Shh
signaling, yet remained in their original spatial domains instead
of migrating laterally as the vMes expands. In addition, I
identified a brief temporal window when the Shh expressing cells
are responsive to Shh signaling (local Shh signaling). I
genetically ablated local Shh signaling to investigate its
significance and uncovered that Shh signaling duration in the vMes
directs cells toward differentiation by promoting cell cycle exit.
Finally, by prolonging the proliferative state of the vMes
progenitors, I showed that mDA neurons bias towards the VTA instead
of the SNc. In conclusion, I defined a developmental program which
coordinates the dynamics of Shh signaling during morphological
expansion of the vMes and a combinatorial temporal genetic code to
control proliferation, differentiation, and cell diversification of
the mDA neurons. These fundamental biological programs that drive
cell fate specification can be applied to cell based therapeutic
approaches for the directed differentiation of pluripotent cells
toward a specific cell fate, not only mDA neurons, but also for
other tissues.
Advisors/Committee Members: Ahn, Sohyun (Director), Zervas, Mark (Director), Connors, Barry (Reader), Mukoyama, Yosuke (Reader), Li, James (Reader).
Subjects/Keywords: Sonic Hedgehog
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hayes, L. N. (2012). Temporal Control of Sonic Hedgehog Signaling for Midbrain
Dopamine Neuron Development. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297700/
Chicago Manual of Style (16th Edition):
Hayes, Lindsay Nicole. “Temporal Control of Sonic Hedgehog Signaling for Midbrain
Dopamine Neuron Development.” 2012. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:297700/.
MLA Handbook (7th Edition):
Hayes, Lindsay Nicole. “Temporal Control of Sonic Hedgehog Signaling for Midbrain
Dopamine Neuron Development.” 2012. Web. 16 Jan 2021.
Vancouver:
Hayes LN. Temporal Control of Sonic Hedgehog Signaling for Midbrain
Dopamine Neuron Development. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:297700/.
Council of Science Editors:
Hayes LN. Temporal Control of Sonic Hedgehog Signaling for Midbrain
Dopamine Neuron Development. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297700/
15.
Barchi, Jonathan R.
Flight path dynamics and spatial memory in the big brown
bat.
Degree: PhD, Neuroscience, 2014, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:386121/
► This work presents several experiments designed to explore the use of spatial memory by echolocating big brown bats (Eptesicus fuscus) through observable flight behavior, specifically…
(more)
▼ This work presents several experiments designed to
explore the use of spatial memory by echolocating big
brown bats
(Eptesicus fuscus) through observable flight behavior, specifically
the development of precisely stereotyped but individual flight
paths through a sparsely cluttered test environment. It was
demonstrated that a small local change to the flight environment
causes changes in flight behavior that are distributed along the
bats’ entire flight paths, suggesting that the bats are using an
internal spatial map to guide their navigation. The temporal
development of flight path stereotypy was measured, and found to be
asymptotically complete by the end of 6 days of daily flight at 5
min. per day. These flight paths were shown to be tolerant to
changes of initial condition, varied by changing the release
location within the flight chamber, and to persist over four weeks
without exposure to the test chamber. When exposed to a slightly
different configuration of obstacles than that one which they were
trained, in the same test chamber, bats maintained their path
precision and quickly adjusted to new flight paths. The precise
stereotypy of the flight paths through space was also observed in
the bats’ velocity profiles throughout the test chamber, suggesting
that these learned flight paths were really learned trajectories
with spatiotemporal content - a learned motor plan - rather than a
simple spatial attractor.
Advisors/Committee Members: Simmons, James (Director), Simmons, Andrea (Reader), Berson, David (Reader), Connors, Barry (Reader), Bandyopadhyay, Promode (Reader).
Subjects/Keywords: bat biosonar
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Barchi, J. R. (2014). Flight path dynamics and spatial memory in the big brown
bat. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:386121/
Chicago Manual of Style (16th Edition):
Barchi, Jonathan R. “Flight path dynamics and spatial memory in the big brown
bat.” 2014. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:386121/.
MLA Handbook (7th Edition):
Barchi, Jonathan R. “Flight path dynamics and spatial memory in the big brown
bat.” 2014. Web. 16 Jan 2021.
Vancouver:
Barchi JR. Flight path dynamics and spatial memory in the big brown
bat. [Internet] [Doctoral dissertation]. Brown University; 2014. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:386121/.
Council of Science Editors:
Barchi JR. Flight path dynamics and spatial memory in the big brown
bat. [Doctoral Dissertation]. Brown University; 2014. Available from: https://repository.library.brown.edu/studio/item/bdr:386121/
16.
Zolnik, Timothy Adam.
Development and Function of Synapses in the Thalamus.
Degree: PhD, Neuroscience, 2012, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:297692/
► The thalamus is essential for normal brain function. The thalamus is widely interconnected with other brain areas, and is best known for relaying sensory information…
(more)
▼ The thalamus is essential for normal brain function.
The thalamus is widely interconnected with other brain areas, and
is best known for relaying sensory information to the cortex,
facilitating communication between various cortical regions, and
participating in important thalamocortical rhythms. An appreciation
of thalamic neurons and synapses is vital to our understanding of
whole-brain function. My thesis begins by exploring the process of
thalamic development. I found that the thalamic network, its
neurons and its inhibitory synapses, undergo dramatic changes in
morphology and physiology as the thalamus matures. I also found
that thalamic neurons lacking the neuronal gap junction isoform
connexin36 (Cx36) are still electrically coupled, although much
more rarely and with properties never before seen in the mammalian
brain. These non-Cx36 electrical synapses are unusual because they
can act like diodes: they pass current preferentially in one
direction. This property had previously only been described in
invertebrate systems. Interestingly, I found that inhibitory
thalamic networks develop differently in the absence of Cx36-based
electrical synapses. I present evidence that inhibitory synapses in
the thalamic reticular nucleus (TRN) and ventrobasal complex (VB)
are affected by Cx36 genotype, and that the inhibitory network
connectivity may rearrange in the Cx36-lacking thalamus. Network
rearrangement may be a compensatory attempt to maintain function
when missing an important neural element. The final section of my
thesis explores the synaptic inputs and outputs of the mature TRN,
examined with optogenetic techniques that overcome the
complications of other techniques used previously. I found that the
inhibitory network within TRN contains sparse, weak connections,
whereas the connections between TRN and VB are strong and common by
comparison. Each glutamatergic input to TRN has very different
short-term plasticity and, surprisingly, were unable to
individually activate metabotropic glutamate receptors (mGluRs);
mGluRs can be strongly and reliably activated by extracellular
electrical stimulation, suggesting that coincident stimulation of
these pathways may be required for mGluR activation in TRN.
Together, these results improve our understanding of how important
thalamic networks develop and how they function in the mature
state.
Advisors/Committee Members: Connors, Barry (Director), Berson, David (Reader), Kauer, Julie (Reader), Chen, Chinfei (Reader).
Subjects/Keywords: electrical synapses
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Zolnik, T. A. (2012). Development and Function of Synapses in the Thalamus. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297692/
Chicago Manual of Style (16th Edition):
Zolnik, Timothy Adam. “Development and Function of Synapses in the Thalamus.” 2012. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:297692/.
MLA Handbook (7th Edition):
Zolnik, Timothy Adam. “Development and Function of Synapses in the Thalamus.” 2012. Web. 16 Jan 2021.
Vancouver:
Zolnik TA. Development and Function of Synapses in the Thalamus. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:297692/.
Council of Science Editors:
Zolnik TA. Development and Function of Synapses in the Thalamus. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297692/
17.
Allen, Summer E.
Cell-specific splicing factors that optimize calcium channel
function.
Degree: PhD, Neuroscience, 2012, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:297693/
► Alternative splicing in the nervous system is an important regulator of neuronal function. CaV2.2 calcium channels control neurotransmission and are extensively alternatively spliced in a…
(more)
▼ Alternative splicing in the nervous system is an
important regulator of neuronal function. CaV2.2 calcium channels
control neurotransmission and are extensively alternatively spliced
in a cell-type specific manner. Splice isoforms of these channels
have distinct basic biophysical properties and unique responses to
G protein-coupled receptors. RNA-binding proteins called splicing
factors regulate the inclusion of alternative exons. There are
several methods that can be used to identify the splicing factors
that regulate inclusion of a particular exon. In this dissertation,
I explore the factors that regulate the inclusion of functionally
important alternative exons within CaV2.2. In Chapter 2, I show
that Nova-2 represses inclusion of exons 31a in CaV2.1 and CaV2.2
in the central nervous system and present evidence that Nova-2
enhances inclusion of an exon which I discovered, exon 24a in
CaV2.1. In Chapter 3, I show that Fox proteins repress inclusion of
exon 18a in CaV2.2 and that this splicing regulation controls the
voltage-independent inhibition of channel proteins by Gs-coupled
receptor agonists. In Chapter 4, I present results from minigene
and bioinformatics analyses that were used to attempt to identify
the splicing factors that regulate the splicing of mutually
exclusive exons 37a and 37b in CaV2.2. Inclusion of exon 37a in
CaV2.2 channels in neurons of dorsal root ganglia allows Gi/o
coupled-receptor agonists, like morphine, to inhibit CaV2.2
channels in a voltage-independent manner. Although I have yet to
identify the splicing factors involved, I present evidence from
minigene studies that suggests a model including a repressor of
exon 37a and an enhancer of exon 37b. Bioinformatic analyses
suggest that hnRNP-A/B and hnRNP-F may regulate inclusion of these
exons. In the discussion chapter I examine how studies such as mine
can provide important insight into cell-specific optimization of
protein function. I also discuss models of splicing regulation and
exciting avenues for future research.
Advisors/Committee Members: Lipscombe, Diane (Director), Connors, Barry (Reader), Fairbrother, William (Reader), Hart, Anne (Reader), Eberwine, James (Reader).
Subjects/Keywords: alternative splicing
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Allen, S. E. (2012). Cell-specific splicing factors that optimize calcium channel
function. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297693/
Chicago Manual of Style (16th Edition):
Allen, Summer E. “Cell-specific splicing factors that optimize calcium channel
function.” 2012. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:297693/.
MLA Handbook (7th Edition):
Allen, Summer E. “Cell-specific splicing factors that optimize calcium channel
function.” 2012. Web. 16 Jan 2021.
Vancouver:
Allen SE. Cell-specific splicing factors that optimize calcium channel
function. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:297693/.
Council of Science Editors:
Allen SE. Cell-specific splicing factors that optimize calcium channel
function. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297693/
18.
Pujala, Avinash.
The neural mechanisms underlying ventral and dorsal
root-evoked fictive locomotion in the neonatal mouse spinal
cord.
Degree: PhD, Neuroscience, 2013, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:320663/
► In this thesis, I made use of the isolated spinal cord preparation of the neonatal mice to investigate the neural mechanisms underlying fictive locomotion. Recently,…
(more)
▼ In this thesis, I made use of the isolated spinal cord
preparation of the neonatal mice to investigate the neural
mechanisms underlying fictive locomotion. Recently, it has been
shown that stimulation of ventral roots (motoneuron axons) produces
fictive locomotion. However, the spinal pathways and
pharmacological mechanisms underlying this phenomenon are unknown.
To further our understanding in this regard, I carried out
experiments to determine if ventral roots activated the locomotor
network in a manner similar to dorsal roots (primary afferents).
When I jointly stimulated dorsal and ventral roots with low
intensity stimuli incapable of eliciting fictive I was unable to
elicit fictive locomotion. This suggested that ventral and dorsal
roots accessed the locomotor network via different sets of
first-order relay interneurons. This was more directly indicated by
recordings from two different relay interneuron populations known
to be contacted by afferents, and to be important for excitation of
the locomotor network. Unlike dorsal roots, ventral roots failed to
elicit monosynaptic responses within these neurons. This raised the
possibility that motor axons and sensory afferents might activate
distinct rhythmogenic networks. To test this idea, I used
interleaved dorsal and ventral root stimulus trains. Such
interleaved stimulus trains elicited robust locomotor-like
activity, suggesting that the two inputs were indeed activating the
same rhythmogenic elements. This was confirmed in a set of
experiments in which the stimulus train began with one root and was
then abruptly switched to the other root. In these experiments,
locomotor-like rhythmic activity continued without interruption,
despite the sudden switch in the stimulation from one root to
another. Collectively these results suggest that dorsal and ventral
root stimuli activate the same rhythmogenic network, but by
exciting different relay interneurons.
In another study, I investigated the pharmacological
mechanisms underlying electrically-elicited fictive locomotion. I
found that fictive locomotion elicited in this manner required
activation of a class of metabotropic glutamate receptors. By
selectively applying pharmacological agents to different parts of
the spinal cord, I was able to uncover evidence suggesting that
this class of metabotropic glutamate receptors played an important
role in the mechanisms of rhythmogenesis.
Advisors/Committee Members: O'Donovan, Michael (Director), Harris-Warrick, Ronald (Reader), McBain, Chris (Reader), Connors, Barry (Reader).
Subjects/Keywords: Fictive locomotion
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pujala, A. (2013). The neural mechanisms underlying ventral and dorsal
root-evoked fictive locomotion in the neonatal mouse spinal
cord. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:320663/
Chicago Manual of Style (16th Edition):
Pujala, Avinash. “The neural mechanisms underlying ventral and dorsal
root-evoked fictive locomotion in the neonatal mouse spinal
cord.” 2013. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:320663/.
MLA Handbook (7th Edition):
Pujala, Avinash. “The neural mechanisms underlying ventral and dorsal
root-evoked fictive locomotion in the neonatal mouse spinal
cord.” 2013. Web. 16 Jan 2021.
Vancouver:
Pujala A. The neural mechanisms underlying ventral and dorsal
root-evoked fictive locomotion in the neonatal mouse spinal
cord. [Internet] [Doctoral dissertation]. Brown University; 2013. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:320663/.
Council of Science Editors:
Pujala A. The neural mechanisms underlying ventral and dorsal
root-evoked fictive locomotion in the neonatal mouse spinal
cord. [Doctoral Dissertation]. Brown University; 2013. Available from: https://repository.library.brown.edu/studio/item/bdr:320663/
19.
quattrochi, lauren E.
The M6 cell: A small-field bistratified photosensitive
ganglion cell.
Degree: PhD, Molecular Pharmacology, Physiology, and
Biotechnology, 2015, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:419536/
► In the late 1800s, Santiago Ramón y Cajal provided the first in-depth description of the cell types that exist within the retina. Even then, he…
(more)
▼ In the late 1800s, Santiago Ramón y Cajal provided the
first in-depth description of the cell types that exist within the
retina. Even then, he realized that there was a vast array of
different cell types residing within a hierarchical and highly
organized fashion within the retina. Over a century later,
scientists are still grappling with how many retinal cell types
exist, their functions, synaptic partners and if applicable,
central projections. Just over a decade ago, the prevalent dogma
was that only two types of photoreceptors existed: rods and cones.
However, recently, pioneers in the field of visual neuroscience
showed that a third class of photoreceptor dwells in the inner
retina in the ganglion cell layer. These new photoreceptors, called
intrinsically photosensitive retinal ganglion cells (ipRGCs), were
capable of endogenous phototransduction. Ganglion photoreceptors
mediate a host of non-image forming visual functions or reflexive
unconscious light-driven behaviors. These behaviors include syncing
the body’s internal clock, pupillary constriction to bright light,
modulating melatonin hormone levels and even influence mood. Since
the discovery of the first ipRGC in 2002, several other subtypes
have emerged. With a growing number of ipRGC subtypes, researchers
are just now broaching what other functional roles they may play in
the visual system. Their functions have now expanded to include
pattern vision and color discrimination (Estevez et al., 2012;
Schmidt et al., 2014; unpublished results). This thesis focuses on
the discovery of another subtype of ipRGC, the M6 cell. Hints that
another subtype was present began when a genetically-engineered,
ipRGC-targeting mouse line revealed substantial labeling in retinal
ganglion cells. However, it was with a new cell-subtype-specific
transgenic line in which we found an ipRGC that did not resemble
any previously described ipRGC types. The aim of this work is to
document the existence of this novel ganglion-cell photoreceptor,
as well as thoroughly characterize its anatomy, physiology and
central innervations.
Advisors/Committee Members: Berson, lauren (Director), Kauer, Julie (Reader), Connors, Barry (Reader), Paradiso, Michael (Reader), Hattar, Samer (Reader).
Subjects/Keywords: ipRGCs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
quattrochi, l. E. (2015). The M6 cell: A small-field bistratified photosensitive
ganglion cell. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419536/
Chicago Manual of Style (16th Edition):
quattrochi, lauren E. “The M6 cell: A small-field bistratified photosensitive
ganglion cell.” 2015. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:419536/.
MLA Handbook (7th Edition):
quattrochi, lauren E. “The M6 cell: A small-field bistratified photosensitive
ganglion cell.” 2015. Web. 16 Jan 2021.
Vancouver:
quattrochi lE. The M6 cell: A small-field bistratified photosensitive
ganglion cell. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:419536/.
Council of Science Editors:
quattrochi lE. The M6 cell: A small-field bistratified photosensitive
ganglion cell. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419536/
20.
Felch, Daniel L.
Cross-Modal Interactions in the Optic Tectum of Xenopus
laevis Tadpoles.
Degree: PhD, Neuroscience, 2015, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:419494/
► Early in the development of Xenopus laevis tadpoles, as the animals become capable of actively navigating their environment, individual neurons in the optic tectum become…
(more)
▼ Early in the development of Xenopus laevis tadpoles,
as the animals become capable of actively navigating their
environment, individual neurons in the optic tectum become
cross-modal. That is, they receive information both from the eye,
via retinal ganglion cell axons, and also from mechanosensory
nuclei in the hindbrain. At present it is unknown how, or even
whether, these two modalities interact in these young tectal
neurons and in the tectal circuit, generally. To begin to address
these questions, I here utilize an isolated-brain preparation to
stimulate these afferent pathways and record, from single cells,
either the excitatory and inhibitory synaptic inputs each receives,
or output that each generates upon activation with cross-modal
stimulus combinations, as well as with uni-modal (within-modality)
combinations. Additionally, to investigate how these relationships
might change over a developmental epoch characterized by extensive
experience-dependent plasticity, I collect data from two groups:
stages 44–46 and stages 48–49. My results show that cross-modal
stimuli do indeed interact in individual neurons of the developing
tectum, such that the magnitude (i.e., total number) and onset
latency of responses are both dependent on inter-stimulus interval.
Furthermore, the data show a selective sensitivity of these
responses for cross-modal combinations, which is
developmentally-regulated. Critically, although the pharmacological
blockade of inhibition abolishes this differential integration of
cross-modal and uni-modal combinations, no differences are seen
between cross-modal and uni-modal effectiveness in the enhancement
of synaptic inhibition, or excitation, at any stage of development.
Additional experiments show a developmentally-regulated increase in
the extent of the recurrent, intra-tectal connections that are
activated by cross-modal combinations, however. These results thus
indicate a mechanism for cross-modal sensitivity that is more
nuanced than the simple balance between excitation and inhibition,
and illustrate important roles for synapse location and dendritic
integration.
Advisors/Committee Members: Aizenman, Carlos (Director), Berson, David (Reader), Kauer, Julie (Reader), Connors, Barry (Reader), Chen, Chinfei (Reader).
Subjects/Keywords: Multisensory
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Felch, D. L. (2015). Cross-Modal Interactions in the Optic Tectum of Xenopus
laevis Tadpoles. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419494/
Chicago Manual of Style (16th Edition):
Felch, Daniel L. “Cross-Modal Interactions in the Optic Tectum of Xenopus
laevis Tadpoles.” 2015. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:419494/.
MLA Handbook (7th Edition):
Felch, Daniel L. “Cross-Modal Interactions in the Optic Tectum of Xenopus
laevis Tadpoles.” 2015. Web. 16 Jan 2021.
Vancouver:
Felch DL. Cross-Modal Interactions in the Optic Tectum of Xenopus
laevis Tadpoles. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:419494/.
Council of Science Editors:
Felch DL. Cross-Modal Interactions in the Optic Tectum of Xenopus
laevis Tadpoles. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419494/
21.
Bellay, Timothy Edward.
Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize
As Neuronal Avalanches.
Degree: PhD, Neuroscience, 2014, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:419370/
► The purpose of this thesis was to identify the cellular mechanisms of the ongoing cortical dynamics called “neuronal avalanches” (NA). NA are the hallmark of…
(more)
▼ The purpose of this thesis was to identify the
cellular mechanisms of the ongoing cortical dynamics called
“neuronal avalanches” (NA). NA are the hallmark of ongoing activity
in the superficial layers of rat, monkey and human cortex found
originally in the local field potential (LFP). NA are precisely
quantified as cascades of synchrony whose size distribution follow
a power law with slope of -3/2. NA signify the balance of
propagation under ongoing dynamics where activity neither dies out
nor explodes and is quantified by a critical branching parameter of
1. Previous work on NA has centered on ambiguous population
measures of synchrony such as the LFP, EEG, fMRI and MEG and thus
the cellular basis of NA remains unknown. In this thesis I tested
the hypothesis that spiking in local groups of pyramidal neurons
(PNs), the major class of cortical excitatory projection neurons,
also organizes as NA. If found true, then the precise scaling laws
derived for NA at mesoscopic and macroscopic levels of the brain
would also apply at the level of the cortical microcircuit. Using
two-photon microscopy, I imaged layer II/III PNs expressing
genetically encoded calcium indicators (GECI) with single AP
sensitivity in awake, head-fixed rats and in spontaneously active
cortex cultures. I found that although single PN spiking was highly
irregular and random, group firing organized into cascades with the
signature of NA. This finding was sensitive to the level of
anesthesia in vivo and to the ratio of excitatory to inhibitory
balance in vitro, supporting the role of NA in maintaining the
healthy, balanced state of ongoing dynamics in the brain.
Furthermore in intracellular recordings of PN in acute slices, I
found that intracellular membrane potential deflections correlated
with specific NA spatial pattern deflections in the LFP. I conclude
that NA signify the precise organization of cortical dynamics at
rest, from the single cell level in local PN groups to the whole
brain. These findings should profoundly inform new theory and
experiments on cellular mechanisms of cortex
function.
Advisors/Committee Members: Plenz, Dietmar (Director), McBain, Chris (Reader), Diamond, Jeffery (Reader), Connors, Barry (Reader), Kanold, Patrick (Reader).
Subjects/Keywords: cortex
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bellay, T. E. (2014). Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize
As Neuronal Avalanches. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419370/
Chicago Manual of Style (16th Edition):
Bellay, Timothy Edward. “Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize
As Neuronal Avalanches.” 2014. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:419370/.
MLA Handbook (7th Edition):
Bellay, Timothy Edward. “Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize
As Neuronal Avalanches.” 2014. Web. 16 Jan 2021.
Vancouver:
Bellay TE. Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize
As Neuronal Avalanches. [Internet] [Doctoral dissertation]. Brown University; 2014. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:419370/.
Council of Science Editors:
Bellay TE. Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize
As Neuronal Avalanches. [Doctoral Dissertation]. Brown University; 2014. Available from: https://repository.library.brown.edu/studio/item/bdr:419370/
22.
Vargish, Geoffrey A.
Investigating the role of cannabinoid type 1 receptors and
vesicular glutamate transporter 3 in cholecystokinin-expressing
interneurons.
Degree: PhD, Neuroscience, 2016, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:674236/
► Precise computation of sensory and contextual information in the mammalian neocortex and hippocampus relies on reciprocally connected networks of excitatory glutamatergic principal cells and inhibitory…
(more)
▼ Precise computation of sensory and contextual
information in the mammalian neocortex and hippocampus relies on
reciprocally connected networks of excitatory glutamatergic
principal cells and inhibitory GABAergic interneurons. Despite
comprising only ~15% of the cortex and hippocampus, GABAergic
interneurons are a remarkably diverse neuronal population, a
characteristic that confers dynamic functionality to this cell
class. In this dissertation, I focus on hippocampal
cholecystokinin-expressing interneurons (CCK INTs) , examining the
role of cannabinoid type 1 receptors (CB1Rs) in CCK INT development
and characterizing a subset of CCK INTs that express vesicular
glutamate transporter 3 (VGLUT3). Using a combination of
immunohistochemistry, electrophysiology and behavioral analysis, I
show that in utero exogenous cannabinoid (CBs) exposure
significantly reduces hippocampal CCK INT density and alters CCK
INT dendritic morphology, resulting in compromised CCK INT-mediated
inhibition in feedforward and feedback pathways of the hippocampal
circuit. Further, I provide evidence that prenatal CB exposure
reduces constitutive CB1R activity and is associated with deficits
in social behavior. These findings provide a potential
cellular/circuit mechanism that may underlie the neurobehavioral
deficits previously observed in humans exposed prenatally to
cannabis. VGLUT3-expression has previously been shown in CCK basket
cells (BCs) of the cortex and hippocampus. However, little is known
about the physiological properties of these cells. Using
VGLUT3-Cre:Ai14-TdTomato mice, I show that, contrary to previous
reports, VGLUT3 is expressed in a cross section of CCK INTs,
capturing both basket and dendrite-targeting morphological
subtypes. In addition, while I show that VGLUT3+ CCK INTs have
intrinsic physiological properties similar to VGLUT3- CCK INTs, and
exhibit synaptic properties characteristic of CCK INTs, I also
provide evidence that VGLUT3+ CCK BCs drive large, polysynaptic
events in neonatal CA3, a function not previously associated with
CCK INTs. These findings provide the first physiological
characterization of VGLUT3+ CCK INTs and suggest a unique
functional role for VGLUT3+ CCK BCs in the developing hippocampus.
Together the findings presented here contribute to our
understanding of the development and function of hippocampal CCK
INTs, providing a foundation for future investigation into the
precise function of these cells during various network and
behavioral states.
Advisors/Committee Members: McBain, Chris (Director), Connors, Barry (Reader), Cameron, Heather (Reader), Khaliq, Zayd (Reader), Higley, Michael (Reader).
Subjects/Keywords: Development
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vargish, G. A. (2016). Investigating the role of cannabinoid type 1 receptors and
vesicular glutamate transporter 3 in cholecystokinin-expressing
interneurons. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:674236/
Chicago Manual of Style (16th Edition):
Vargish, Geoffrey A. “Investigating the role of cannabinoid type 1 receptors and
vesicular glutamate transporter 3 in cholecystokinin-expressing
interneurons.” 2016. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:674236/.
MLA Handbook (7th Edition):
Vargish, Geoffrey A. “Investigating the role of cannabinoid type 1 receptors and
vesicular glutamate transporter 3 in cholecystokinin-expressing
interneurons.” 2016. Web. 16 Jan 2021.
Vancouver:
Vargish GA. Investigating the role of cannabinoid type 1 receptors and
vesicular glutamate transporter 3 in cholecystokinin-expressing
interneurons. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:674236/.
Council of Science Editors:
Vargish GA. Investigating the role of cannabinoid type 1 receptors and
vesicular glutamate transporter 3 in cholecystokinin-expressing
interneurons. [Doctoral Dissertation]. Brown University; 2016. Available from: https://repository.library.brown.edu/studio/item/bdr:674236/
23.
Cao, Vania Yu.
Experience-dependent Activation of Arc Expression in
Individual Frontal Cortical Neurons During Motor Training.
Degree: PhD, Neuroscience, 2014, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:386133/
► An important goal in neuroscience is to understand how experience affects the selection, execution and maintenance of different action plans, and how this is reflected…
(more)
▼ An important goal in neuroscience is to understand how
experience affects the selection, execution and maintenance of
different action plans, and how this is reflected in neural
activity. The frontal cortex plays an important role in motor
planning and the output of behavior, making it a particular region
of interest. Elucidating how neural ensembles in frontal cortex
respond and change in a behaving animal would contribute to a basic
but important understanding of how the brain adapts to different
environments and situations, and in the future, how aberrant neural
circuitry may contribute to abnormal behaviors. We identified and
characterized the experience-dependent molecular dynamics of Arc, a
plasticity-related immediate early gene, within individual frontal
cortical neurons over days. Chapter 1 discusses the state of the
current understanding of frontal cortex involvement in motor tasks,
along with methods to study neuronal ensemble dynamics. Chapter 2
investigates the role of the murine M2 region of the frontal cortex
in the performance of a motor task, the accelerating rotarod task.
A longitudinal in vivo imaging and behavioral protocol which can be
used to study Arc expression dynamics in frontal cortical neurons
are outlined in Chapter 3. Repeated in vivo imaging of Arc
expression dynamics in frontal cortical neurons during different
behavioral conditions is conducted in Chapter 4. The data are
summarized and discussed, alongside future directions, in Chapter
5.
Advisors/Committee Members: Wang, Kuan (Director), Costa, Rui (Director), Zuo, Yi (Reader), Belluscio, Leonardo (Reader), Connors, Barry (Reader).
Subjects/Keywords: Arc
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Cao, V. Y. (2014). Experience-dependent Activation of Arc Expression in
Individual Frontal Cortical Neurons During Motor Training. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:386133/
Chicago Manual of Style (16th Edition):
Cao, Vania Yu. “Experience-dependent Activation of Arc Expression in
Individual Frontal Cortical Neurons During Motor Training.” 2014. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:386133/.
MLA Handbook (7th Edition):
Cao, Vania Yu. “Experience-dependent Activation of Arc Expression in
Individual Frontal Cortical Neurons During Motor Training.” 2014. Web. 16 Jan 2021.
Vancouver:
Cao VY. Experience-dependent Activation of Arc Expression in
Individual Frontal Cortical Neurons During Motor Training. [Internet] [Doctoral dissertation]. Brown University; 2014. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:386133/.
Council of Science Editors:
Cao VY. Experience-dependent Activation of Arc Expression in
Individual Frontal Cortical Neurons During Motor Training. [Doctoral Dissertation]. Brown University; 2014. Available from: https://repository.library.brown.edu/studio/item/bdr:386133/
24.
Bell, Mark R.
A neuroprotective role for putrescine in a Xenopus tadpole
seizure model.
Degree: PhD, Neuroscience, 2012, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:297697/
► Polyamines are endogenous molecules involved in cell damage following neurological insults, although it is unclear whether polyamines reduce or exacerbate this damage. We used a…
(more)
▼ Polyamines are endogenous molecules involved in cell
damage following neurological insults, although it is unclear
whether polyamines reduce or exacerbate this damage. We used a
developmental seizure model in which we exposed Xenopus laevis
tadpoles to pentylenetetrazole (PTZ), a known convulsant. We found
that, after an initial PTZ exposure, seizure onset times were
delayed in response to a second PTZ exposure 4 h later. This
protective effect was a result of activity-dependent increases in
synthesis of putrescine, the simplest polyamine. Unlike more
complex polyamines that directly modulate ion channels, putrescine
exerted its effect by altering the balance of excitation to
inhibition. Tectal neuron recordings, 4 h after the initial
seizure, revealed an elevated frequency of GABAergic spontaneous
inhibitory postsynaptic currents. Our data suggest that this effect
is mediated by an atypical pathway that converts putrescine into
GABA, which then activates presynaptic GABAB receptors, suggesting
that polyamines have a previously unknown neuroprotective role in
the developing brain.
Advisors/Committee Members: Aizenman, Carlos (Director), Kauer, Julie (Reader), Connors, Barry (Reader), Jensen, Frances (Reader).
Subjects/Keywords: seizures
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bell, M. R. (2012). A neuroprotective role for putrescine in a Xenopus tadpole
seizure model. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297697/
Chicago Manual of Style (16th Edition):
Bell, Mark R. “A neuroprotective role for putrescine in a Xenopus tadpole
seizure model.” 2012. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:297697/.
MLA Handbook (7th Edition):
Bell, Mark R. “A neuroprotective role for putrescine in a Xenopus tadpole
seizure model.” 2012. Web. 16 Jan 2021.
Vancouver:
Bell MR. A neuroprotective role for putrescine in a Xenopus tadpole
seizure model. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:297697/.
Council of Science Editors:
Bell MR. A neuroprotective role for putrescine in a Xenopus tadpole
seizure model. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297697/
25.
Wagner, Fabien B.
Dynamics of Epileptic Seizure Transition Investigated with
Intracortical Microelectrode Arrays and Optogenetic
Neuromodulation.
Degree: PhD, Neuroscience, 2015, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:419382/
► Epilepsy is a common neurological disorder characterized by the recurrence of spontaneous seizures. However, the mechanisms of transition into seizures are still unclear. A better…
(more)
▼ Epilepsy is a common neurological disorder
characterized by the recurrence of spontaneous seizures. However,
the mechanisms of transition into seizures are still unclear. A
better understanding relies on the development of new technologies
to study neural activity at multiple scales. In this thesis, I
first developed experimental and computational tools to study
neocortical spatiotemporal dynamics in freely moving epileptic
rats. These tools enable recordings of neural signals at various
scales, from single neurons to local field potentials, both during
spontaneous activity and in response to external optogenetic
perturbation. I then applied these techniques to the study of
primary generalized epilepsy, where the transition into the ictal
state occurs particularly abruptly and synchronously across the
brain. I used optogenetics to causally test the hypothesis that
rhythmic population bursting in a local neocortical region can
rapidly trigger primary generalized absence seizures. Most previous
studies have been purely correlational, and it remains
controversial whether afterdischarges induced via rhythmic
sensory/electrical stimulation mimic actual spontaneous seizures,
especially regarding their spatiotemporal dynamics. Here, I used a
novel combination of intracortical optogenetic stimulation and
microelectrode array recordings in freely moving WAG/Rij rats, a
model of absence epilepsy with a presumed cortical focus in the
somatosensory cortex (SI). Brief rhythmic bursting, evoked by
optical stimulation of SI excitatory cells at frequencies around 10
Hz, induced self-sustained seizure-like afterdischarges with about
10% probability. The probability of inducing afterdischarges was
strongly frequency-dependent, with a peak at 10 Hz. Furthermore,
afterdischarges and spontaneous seizures had similar spectral
characteristics and durations, indicating common mechanisms. Local
field potential power before stimulation and the amplitude of
optically-evoked bursts during stimulation both predicted
afterdischarge induction, demonstrating a modulatory effect of
ongoing brain states and neural excitability. Evoked bursts during
stimulation propagated as cortical waves, likely reaching the
cortical focus and inducing afterdischarges after stimulation was
terminated. Importantly, self-sustained afterdischarges propagated
with the same direction and spatiotemporal dynamics as spontaneous
seizures. These findings demonstrate that local rhythmic bursting
in neocortex at particular frequencies, under susceptible ongoing
brain states, can trigger primary generalized absence seizures with
stereotypical spatiotemporal dynamics.
Advisors/Committee Members: Nurmikko, Arto (Director), Truccolo, Wilson (Reader), Connors, Barry (Reader), Hochberg, Leigh (Reader), Moore, Christopher (Reader).
Subjects/Keywords: microelectrode arrays
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wagner, F. B. (2015). Dynamics of Epileptic Seizure Transition Investigated with
Intracortical Microelectrode Arrays and Optogenetic
Neuromodulation. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419382/
Chicago Manual of Style (16th Edition):
Wagner, Fabien B. “Dynamics of Epileptic Seizure Transition Investigated with
Intracortical Microelectrode Arrays and Optogenetic
Neuromodulation.” 2015. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:419382/.
MLA Handbook (7th Edition):
Wagner, Fabien B. “Dynamics of Epileptic Seizure Transition Investigated with
Intracortical Microelectrode Arrays and Optogenetic
Neuromodulation.” 2015. Web. 16 Jan 2021.
Vancouver:
Wagner FB. Dynamics of Epileptic Seizure Transition Investigated with
Intracortical Microelectrode Arrays and Optogenetic
Neuromodulation. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:419382/.
Council of Science Editors:
Wagner FB. Dynamics of Epileptic Seizure Transition Investigated with
Intracortical Microelectrode Arrays and Optogenetic
Neuromodulation. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419382/
26.
Shaikhouni, Ammar M.
Sensory Input To The Human Primary Motor Cortex After Long
Term Damage To Motor Output Pathways: Implications For The Design
Of Neural Interface Devices.
Degree: PhD, Neuroscience, 2011, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11405/
► The primate precentral cortex receives somatosensory inputs, but very little is known about the influence of these inputs on motor cortical activity patterns in humans.…
(more)
▼ The primate precentral cortex receives somatosensory
inputs, but very little is known about the influence of these
inputs on motor cortical activity patterns in humans. To determine
whether sensory inputs continue to influence MI neurons after
injury to its descending pathways, we examined the local field
(LFP) and action potential responses of precentral neurons of a
54-year-old woman (S3) with tetraplegia due to pontine infarction.
Neural activity was recorded using microelectrodes placed into the
dominant arm MI. Many single units responded to passive
manipulation and intended movement of the contralateral arm.
Similarly, passive movement modulated LFP in both time and
frequency domains. In the time domain passive movement of S3
contralateral arm joints was associated with a somatosensory evoked
potential (SSEP). In the frequency domain we observed modulation of
power in four frequency bands: <5Hz, 15-30Hz, 40-55Hz, and
65-100Hz. LFP and spiking responses were also observed during
intended joint movement. However, the sensory and intended
responses of joints varied. Two-thirds of units had either
completely or partially overlapping passive and intended joint
movement representations while one-third of units showed no
relationship between their responses during passive and attempted
movements. Decoding experiments revealed that we can predict the
passive or attempted movements using classifiers based on
population spiking activity as well as LFP activity. However, a
decoder built with activity in one of those conditions cannot be
used to decode the activity in the other suggesting that passive
and active movements representation is different. Significantly, we
show that changes in posture can degrade the performance of
attempted movement decoders. Our results indicate that sensory
input is reflected in both spiking and LFP activity in MI. This
input has the potential to influence online decoding of motor
intentions and must be considered in the design of neural interface
systems.
Advisors/Committee Members: Donoghue, John (Director), Hochberg, Leigh (Reader), Sanes, Jerome (Reader), Connors, Barry (Reader), Cash, Sydney (Reader).
Subjects/Keywords: LFP
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shaikhouni, A. M. (2011). Sensory Input To The Human Primary Motor Cortex After Long
Term Damage To Motor Output Pathways: Implications For The Design
Of Neural Interface Devices. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11405/
Chicago Manual of Style (16th Edition):
Shaikhouni, Ammar M. “Sensory Input To The Human Primary Motor Cortex After Long
Term Damage To Motor Output Pathways: Implications For The Design
Of Neural Interface Devices.” 2011. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:11405/.
MLA Handbook (7th Edition):
Shaikhouni, Ammar M. “Sensory Input To The Human Primary Motor Cortex After Long
Term Damage To Motor Output Pathways: Implications For The Design
Of Neural Interface Devices.” 2011. Web. 16 Jan 2021.
Vancouver:
Shaikhouni AM. Sensory Input To The Human Primary Motor Cortex After Long
Term Damage To Motor Output Pathways: Implications For The Design
Of Neural Interface Devices. [Internet] [Doctoral dissertation]. Brown University; 2011. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:11405/.
Council of Science Editors:
Shaikhouni AM. Sensory Input To The Human Primary Motor Cortex After Long
Term Damage To Motor Output Pathways: Implications For The Design
Of Neural Interface Devices. [Doctoral Dissertation]. Brown University; 2011. Available from: https://repository.library.brown.edu/studio/item/bdr:11405/
27.
Sugden, Arthur U.
Diverse subtypes of fast-spiking inhibitory neurons in
neocortex.
Degree: PhD, Molecular Biology, Cell Biology, and
Biochemistry, 2015, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:419451/
► Inhibitory interneurons are essential for normal cortical function. They prevent seizures, regulate temporal and spatial coding, and generate oscillations and synchrony in pyramidal cells. The…
(more)
▼ Inhibitory interneurons are essential for normal
cortical function. They prevent seizures, regulate temporal and
spatial coding, and generate oscillations and synchrony in
pyramidal cells. The largest subtype of inhibitory interneurons is
fast-spiking (FS) cells, which mediate feedforward inhibition and
have been implicated in the generation of gamma oscillations, the
oscillations that may bind a percept together as it passes through
groups of neurons. FS cells are canonically marked by the
calcium-binding protein parvalbumin (PV), whose levels have been
linked to synaptic plasticity. Like-types of adult neocortical
inhibitory neurons are linked by gap junctions with a probability
of greater than 50% within 50 microns. FS cells are linked by gap
junctions, and these gap junctions have long been thought to add to
the generation of gamma oscillations. In this dissertation I have
asked two questions. First, ventral postrhinal cortex, a subset of
the parahippocampal region, lacks canonical PV-expressing FS cells.
Within this area, it has been possible to ask how is inhibition
altered in a neocortical region lacking canonical FS cells? Second,
using a two-pronged approach of in vitro electrophysiology and a
computational model, I have asked what roles do gap junctions play
in neocortical gamma oscillations? In examining these problems, I
have found three results. First, the commonly-stated overlap
between parvalbumin (PV) and FS cells does not apply in ventral
postrhinal cortex. The majority of FS cells in this region are
PV-negative, and these cells extend into neighboring cortex with
canonical FS cells. Second, the absence of canonical FS cells from
vPOR and the corresponding decrease in inhibitory cell density does
not decrease total inhibition onto excitatory cells, due to
decreased inhibition onto inhibitory cells in vPOR. Third, gamma
oscillations do not require gap junctions in neocortex, unless
compensation in RS cells for the lack of gap junctions in
inhibitory cells is masking the effect.
Advisors/Committee Members: Connors, Barry (Director), Cruikshank, Scott (Director), Barnea, Gilad (Reader), Berson, David (Reader), Jaworski, Alexander (Reader), Harwell, Corey (Reader).
Subjects/Keywords: inhibitory
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sugden, A. U. (2015). Diverse subtypes of fast-spiking inhibitory neurons in
neocortex. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:419451/
Chicago Manual of Style (16th Edition):
Sugden, Arthur U. “Diverse subtypes of fast-spiking inhibitory neurons in
neocortex.” 2015. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:419451/.
MLA Handbook (7th Edition):
Sugden, Arthur U. “Diverse subtypes of fast-spiking inhibitory neurons in
neocortex.” 2015. Web. 16 Jan 2021.
Vancouver:
Sugden AU. Diverse subtypes of fast-spiking inhibitory neurons in
neocortex. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:419451/.
Council of Science Editors:
Sugden AU. Diverse subtypes of fast-spiking inhibitory neurons in
neocortex. [Doctoral Dissertation]. Brown University; 2015. Available from: https://repository.library.brown.edu/studio/item/bdr:419451/
28.
Lippman, Jocelyn Jean.
Forming the tripartite synapse: Development of glial
ensheathment and its role in synaptogenesis.
Degree: PhD, Neuroscience, 2008, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:11021/
► Over the last few decades, scientists have begun to fully recognize the importance of astroglia in synaptic formation and function. The perisynaptic glial processes are…
(more)
▼ Over the last few decades, scientists have begun to
fully recognize the importance of astroglia in synaptic formation
and function. The perisynaptic glial processes are in an ideal
location to exert influence over the synapses, but how these
astrocytic processes become associated with synaptic structures
during development is still not well understood. Here we analyzed
the pattern of growth of the processes extending off the main
Bergmann glial (BG) shafts during synaptogenesis in the cerebellum.
We found that during this period, BG process outgrowth was
correlated with increased ensheathment of dendritic spines. In
addition, two-photon time-lapse imaging revealed that BG processes
were highly dynamic, and processes became more stable as the period
of spine ensheathment progressed. While process motility was
dependent on actin polymerization, activity of cytoskeletal
regulators Rac1 and RhoG did not play a role in glial process
dynamics or density, but was critical for maintaining process
length. We extended this finding to probe the relationship between
glial process morphology and ensheathment, finding that shortening
the processes by blocking rac1 activity leads to decreased coverage
of the spine. Furthermore, we found that experimentally retracting
BG processes towards the end of the period of synaptogenesis, and
therefore lowering level of synaptic ensheathment, did not alter
dendritic spine motility but resulted in these areas having more
synapses than in controls with normal levels of ensheathment. These
analyses reveal how BG processes grow to surround synaptic
structures, elucidate the importance of BG process structure for
proper development of synaptic ensheathment, and reveal a role for
ensheathment in the regulation of synapse number.
Advisors/Committee Members: Dunaevsky, Anna (Director), Connors, Barry (Reader), Berson, David (Reader), Aizenman, Carlos (Reader), Hatten, Mary Beth (Reader).
Subjects/Keywords: cerebellar development
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lippman, J. J. (2008). Forming the tripartite synapse: Development of glial
ensheathment and its role in synaptogenesis. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11021/
Chicago Manual of Style (16th Edition):
Lippman, Jocelyn Jean. “Forming the tripartite synapse: Development of glial
ensheathment and its role in synaptogenesis.” 2008. Doctoral Dissertation, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:11021/.
MLA Handbook (7th Edition):
Lippman, Jocelyn Jean. “Forming the tripartite synapse: Development of glial
ensheathment and its role in synaptogenesis.” 2008. Web. 16 Jan 2021.
Vancouver:
Lippman JJ. Forming the tripartite synapse: Development of glial
ensheathment and its role in synaptogenesis. [Internet] [Doctoral dissertation]. Brown University; 2008. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:11021/.
Council of Science Editors:
Lippman JJ. Forming the tripartite synapse: Development of glial
ensheathment and its role in synaptogenesis. [Doctoral Dissertation]. Brown University; 2008. Available from: https://repository.library.brown.edu/studio/item/bdr:11021/
.