+publisher:"Brown University" +contributor:("Connors, Barry")

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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APA (6^th 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 (16^th Edition):

Blaeser, Andrew S. “Optical Interrogation of the Spontaneous Dynamics of Prefrontal Cortical Networks.” 2015. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:419386/.

MLA Handbook (7^th Edition):

Blaeser, Andrew S. “Optical Interrogation of the Spontaneous Dynamics of Prefrontal Cortical Networks.” 2015. Web. 22 Oct 2019.

Vancouver:

Blaeser AS. Optical Interrogation of the Spontaneous Dynamics of Prefrontal Cortical Networks. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Xu, Heng. “Optical Recording and Photo Modulation in the Study of Dynamics in Neural Circuits.” 2010. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:11119/.

MLA Handbook (7^th Edition):

Xu, Heng. “Optical Recording and Photo Modulation in the Study of Dynamics in Neural Circuits.” 2010. Web. 22 Oct 2019.

Vancouver:

Xu H. Optical Recording and Photo Modulation in the Study of Dynamics in Neural Circuits. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2019 Oct 22]. 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)

Subjects/Keywords: optogenetics; channelrhodopsin(ChR2); optrode; microelectrode array; neural stimulation; retinal recording

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APA (6^th 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 (16^th Edition):

Zhang, Jiayi. “Optical Stimulation and Spatiotemporal Electrical Recording ni Genetically Targeted Brain Tissue.” 2009. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:201/.

MLA Handbook (7^th Edition):

Zhang, Jiayi. “Optical Stimulation and Spatiotemporal Electrical Recording ni Genetically Targeted Brain Tissue.” 2009. Web. 22 Oct 2019.

Vancouver:

Zhang J. Optical Stimulation and Spatiotemporal Electrical Recording ni Genetically Targeted Brain Tissue. [Internet] [Doctoral dissertation]. Brown University; 2009. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Kim, Jennifer A. “Febrile Seizures, Hyperthermia and Hippocampal Neuron Physiology.” 2010. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:11064/.

MLA Handbook (7^th Edition):

Kim, Jennifer A. “Febrile Seizures, Hyperthermia and Hippocampal Neuron Physiology.” 2010. Web. 22 Oct 2019.

Vancouver:

Kim JA. Febrile Seizures, Hyperthermia and Hippocampal Neuron Physiology. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Neske, Garrett T. “Roles of diverse inhibitory interneurons and mechanisms of synchronized inhibition in active cortical networks.” 2016. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:674130/.

MLA Handbook (7^th Edition):

Neske, Garrett T. “Roles of diverse inhibitory interneurons and mechanisms of synchronized inhibition in active cortical networks.” 2016. Web. 22 Oct 2019.

Vancouver:

Neske GT. Roles of diverse inhibitory interneurons and mechanisms of synchronized inhibition in active cortical networks. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Ahmed, Omar Jamil. “Interpreting the Rhythms of the Hippocampus and Neocortex.” 2010. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:11044/.

MLA Handbook (7^th Edition):

Ahmed, Omar Jamil. “Interpreting the Rhythms of the Hippocampus and Neocortex.” 2010. Web. 22 Oct 2019.

Vancouver:

Ahmed OJ. Interpreting the Rhythms of the Hippocampus and Neocortex. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Urabe, Hayato. “Optical Elucidation of Neural Microcircuitry.” 2009. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:216/.

MLA Handbook (7^th Edition):

Urabe, Hayato. “Optical Elucidation of Neural Microcircuitry.” 2009. Web. 22 Oct 2019.

Vancouver:

Urabe H. Optical Elucidation of Neural Microcircuitry. [Internet] [Doctoral dissertation]. Brown University; 2009. [cited 2019 Oct 22]. 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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APA (6^th 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 (16^th Edition):

Normand, Elizabeth A. “Genetic disruption of the thalamus in the context of the neurodevelopmental disorder Tuberous Sclerosis.” 2013. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:320574/.

MLA Handbook (7^th Edition):

Normand, Elizabeth A. “Genetic disruption of the thalamus in the context of the neurodevelopmental disorder Tuberous Sclerosis.” 2013. Web. 22 Oct 2019.

Vancouver:

Normand EA. Genetic disruption of the thalamus in the context of the neurodevelopmental disorder Tuberous Sclerosis. [Internet] [Doctoral dissertation]. Brown University; 2013. [cited 2019 Oct 22]. 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)

Subjects/Keywords: melanopsin phototransduction

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APA (6^th 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 (16^th Edition):

Graham, Dustin M. “Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in the Mammalian Eye.” 2009. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:94/.

MLA Handbook (7^th Edition):

Graham, Dustin M. “Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in the Mammalian Eye.” 2009. Web. 22 Oct 2019.

Vancouver:

Graham DM. Melanopsin Ganglion Cell Phototransduction: A Bit of Fly in the Mammalian Eye. [Internet] [Doctoral dissertation]. Brown University; 2009. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Hynes, Jacqueline Bernadette. “Network Interactions during Contextual Information Processing in Macaque Primary Visual Cortex.” 2016. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:674342/.

MLA Handbook (7^th Edition):

Hynes, Jacqueline Bernadette. “Network Interactions during Contextual Information Processing in Macaque Primary Visual Cortex.” 2016. Web. 22 Oct 2019.

Vancouver:

Hynes JB. Network Interactions during Contextual Information Processing in Macaque Primary Visual Cortex. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2019 Oct 22]. 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 (6^th 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 (16^th 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 October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:419492/.

MLA Handbook (7^th Edition):

Fogerson, Patricia M. “Output streams of intrinsically photosensitive ganglion cells: Distinct types supply different visual and limbic networks.” 2015. Web. 22 Oct 2019.

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 2019 Oct 22]. 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)

Subjects/Keywords: Gap junctions

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APA (6^th 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 (16^th Edition):

Dobson, Lauren G. “Loss of connexin36-mediated gap junctions impairs odor discrimination in mice.” 2016. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:674201/.

MLA Handbook (7^th Edition):

Dobson, Lauren G. “Loss of connexin36-mediated gap junctions impairs odor discrimination in mice.” 2016. Web. 22 Oct 2019.

Vancouver:

Dobson LG. Loss of connexin36-mediated gap junctions impairs odor discrimination in mice. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Lee, Seung-Chan. “Development, organization and function of electrical synapses in the thalamus.” 2010. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:11096/.

MLA Handbook (7^th Edition):

Lee, Seung-Chan. “Development, organization and function of electrical synapses in the thalamus.” 2010. Web. 22 Oct 2019.

Vancouver:

Lee S. Development, organization and function of electrical synapses in the thalamus. [Internet] [Doctoral dissertation]. Brown University; 2010. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Hayes, Lindsay Nicole. “Temporal Control of Sonic Hedgehog Signaling for Midbrain Dopamine Neuron Development.” 2012. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:297700/.

MLA Handbook (7^th Edition):

Hayes, Lindsay Nicole. “Temporal Control of Sonic Hedgehog Signaling for Midbrain Dopamine Neuron Development.” 2012. Web. 22 Oct 2019.

Vancouver:

Hayes LN. Temporal Control of Sonic Hedgehog Signaling for Midbrain Dopamine Neuron Development. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2019 Oct 22]. 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)

Subjects/Keywords: bat biosonar

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APA (6^th 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 (16^th Edition):

Barchi, Jonathan R. “Flight path dynamics and spatial memory in the big brown bat.” 2014. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:386121/.

MLA Handbook (7^th Edition):

Barchi, Jonathan R. “Flight path dynamics and spatial memory in the big brown bat.” 2014. Web. 22 Oct 2019.

Vancouver:

Barchi JR. Flight path dynamics and spatial memory in the big brown bat. [Internet] [Doctoral dissertation]. Brown University; 2014. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Zolnik, Timothy Adam. “Development and Function of Synapses in the Thalamus.” 2012. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:297692/.

MLA Handbook (7^th Edition):

Zolnik, Timothy Adam. “Development and Function of Synapses in the Thalamus.” 2012. Web. 22 Oct 2019.

Vancouver:

Zolnik TA. Development and Function of Synapses in the Thalamus. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Allen, Summer E. “Cell-specific splicing factors that optimize calcium channel function.” 2012. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:297693/.

MLA Handbook (7^th Edition):

Allen, Summer E. “Cell-specific splicing factors that optimize calcium channel function.” 2012. Web. 22 Oct 2019.

Vancouver:

Allen SE. Cell-specific splicing factors that optimize calcium channel function. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2019 Oct 22]. 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 (6^th 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 (16^th 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 October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:320663/.

MLA Handbook (7^th Edition):

Pujala, Avinash. “The neural mechanisms underlying ventral and dorsal root-evoked fictive locomotion in the neonatal mouse spinal cord.” 2013. Web. 22 Oct 2019.

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 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

quattrochi, lauren E. “The M6 cell: A small-field bistratified photosensitive ganglion cell.” 2015. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:419536/.

MLA Handbook (7^th Edition):

quattrochi, lauren E. “The M6 cell: A small-field bistratified photosensitive ganglion cell.” 2015. Web. 22 Oct 2019.

Vancouver:

quattrochi lE. The M6 cell: A small-field bistratified photosensitive ganglion cell. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Felch, Daniel L. “Cross-Modal Interactions in the Optic Tectum of Xenopus laevis Tadpoles.” 2015. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:419494/.

MLA Handbook (7^th Edition):

Felch, Daniel L. “Cross-Modal Interactions in the Optic Tectum of Xenopus laevis Tadpoles.” 2015. Web. 22 Oct 2019.

Vancouver:

Felch DL. Cross-Modal Interactions in the Optic Tectum of Xenopus laevis Tadpoles. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Bellay, Timothy Edward. “Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize As Neuronal Avalanches.” 2014. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:419370/.

MLA Handbook (7^th Edition):

Bellay, Timothy Edward. “Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize As Neuronal Avalanches.” 2014. Web. 22 Oct 2019.

Vancouver:

Bellay TE. Ongoing Dynamics of Layer II/III Pyramidal Neurons Organize As Neuronal Avalanches. [Internet] [Doctoral dissertation]. Brown University; 2014. [cited 2019 Oct 22]. 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 (6^th 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 (16^th 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 October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:674236/.

MLA Handbook (7^th Edition):

Vargish, Geoffrey A. “Investigating the role of cannabinoid type 1 receptors and vesicular glutamate transporter 3 in cholecystokinin-expressing interneurons.” 2016. Web. 22 Oct 2019.

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 2019 Oct 22]. 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)

Subjects/Keywords: Arc

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APA (6^th 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 (16^th Edition):

Cao, Vania Yu. “Experience-dependent Activation of Arc Expression in Individual Frontal Cortical Neurons During Motor Training.” 2014. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:386133/.

MLA Handbook (7^th Edition):

Cao, Vania Yu. “Experience-dependent Activation of Arc Expression in Individual Frontal Cortical Neurons During Motor Training.” 2014. Web. 22 Oct 2019.

Vancouver:

Cao VY. Experience-dependent Activation of Arc Expression in Individual Frontal Cortical Neurons During Motor Training. [Internet] [Doctoral dissertation]. Brown University; 2014. [cited 2019 Oct 22]. 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)

Subjects/Keywords: seizures

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APA (6^th 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 (16^th Edition):

Bell, Mark R. “A neuroprotective role for putrescine in a Xenopus tadpole seizure model.” 2012. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:297697/.

MLA Handbook (7^th Edition):

Bell, Mark R. “A neuroprotective role for putrescine in a Xenopus tadpole seizure model.” 2012. Web. 22 Oct 2019.

Vancouver:

Bell MR. A neuroprotective role for putrescine in a Xenopus tadpole seizure model. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Wagner, Fabien B. “Dynamics of Epileptic Seizure Transition Investigated with Intracortical Microelectrode Arrays and Optogenetic Neuromodulation.” 2015. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:419382/.

MLA Handbook (7^th Edition):

Wagner, Fabien B. “Dynamics of Epileptic Seizure Transition Investigated with Intracortical Microelectrode Arrays and Optogenetic Neuromodulation.” 2015. Web. 22 Oct 2019.

Vancouver:

Wagner FB. Dynamics of Epileptic Seizure Transition Investigated with Intracortical Microelectrode Arrays and Optogenetic Neuromodulation. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2019 Oct 22]. 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 (6^th 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 (16^th 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 October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:11405/.

MLA Handbook (7^th 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. 22 Oct 2019.

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 2019 Oct 22]. 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 (6^th 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 (16^th Edition):

Sugden, Arthur U. “Diverse subtypes of fast-spiking inhibitory neurons in neocortex.” 2015. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:419451/.

MLA Handbook (7^th Edition):

Sugden, Arthur U. “Diverse subtypes of fast-spiking inhibitory neurons in neocortex.” 2015. Web. 22 Oct 2019.

Vancouver:

Sugden AU. Diverse subtypes of fast-spiking inhibitory neurons in neocortex. [Internet] [Doctoral dissertation]. Brown University; 2015. [cited 2019 Oct 22]. 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)

Subjects/Keywords: cerebellar development

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APA (6^th 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 (16^th Edition):

Lippman, Jocelyn Jean. “Forming the tripartite synapse: Development of glial ensheathment and its role in synaptogenesis.” 2008. Doctoral Dissertation, Brown University. Accessed October 22, 2019. https://repository.library.brown.edu/studio/item/bdr:11021/.

MLA Handbook (7^th Edition):

Lippman, Jocelyn Jean. “Forming the tripartite synapse: Development of glial ensheathment and its role in synaptogenesis.” 2008. Web. 22 Oct 2019.

Vancouver:

Lippman JJ. Forming the tripartite synapse: Development of glial ensheathment and its role in synaptogenesis. [Internet] [Doctoral dissertation]. Brown University; 2008. [cited 2019 Oct 22]. 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/

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