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You searched for +publisher:"Rutgers University" +contributor:("Paradiso, Kenneth"). Showing records 1 – 3 of 3 total matches.

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Rutgers University

1. Clarke, Stephen G., 1988-. The ups and downs of electrical activity in the brain: studying how components of the action potential waveform modulate neurotransmission.

Degree: MS, Biomedical Engineering, 2013, Rutgers University

Action potentials (APs) are travelling waves of electrical activity in neurons composed of a rapid increase in membrane potential called a depolarization, followed by a repolarizing phase returning the membrane to a resting potential. Although APs are often thought of as all-or-nothing events, this is not necessarily the case. The AP waveform is generated by voltage-gated sodium and potassium channels whose composition, density and activity vary between and within neurons based on the function and output of that neuron. In addition to signal propagation, the purpose of an AP is to initiate the cascade of neurotransmitter release, beginning with the opening of voltage-gated calcium channels activated by the AP. Here, we set out to better determine how AP waveforms affect calcium influx and subsequent neurotransmitter release. The patch clamp technique has emerged as the best method to measure and study macroscopic electrical activity in neurons. Presynaptic APs at most synapses in the brain are difficult to study due to the small size of most presynaptic terminals. However, the calyx of Held synapse in the mammalian auditory brainstem is large enough to allow patch clamp recordings. In mouse brain slices, perfused with sodium and potassium channel blockers, various iii voltage protocols were tested to determine how modulation of AP kinetics alter calcium activity. First, various depolarization and repolarization rates were studied with test pulses of equivalent stimulus duration at 1 ms, showing that a repolarization/depolarization ratio between 1.5 and 2.3 is optimal for eliciting calcium influx. Additionally, depolarizations that follow the AP were studied and found to have no appreciable effect on calcium activity within the physiological range for AP durations in this neuron. However, if the repolarization rate is sufficiently fast, these currents were found to significantly alter the timing and magnitude of calcium influx. Finally, the AP was shown to minimize calcium channel inactivation to promote consistent and reliable neurotransmitter release. These findings will serve as the starting point for future work performing simultaneous pre- and postsynaptic patch clamp recordings to study transmission. This work promotes a better understanding of how AP kinetics affect calcium channel activity and thus neurotransmission. Advisors/Committee Members: Paradiso, Kenneth (chair), Firestein, Bonnie (internal member), Shreiber, David (internal member).

Subjects/Keywords: Action potentials (Electrophysiology); Brain – Electric properties; Neural transmission

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APA (6th Edition):

Clarke, Stephen G., 1. (2013). The ups and downs of electrical activity in the brain: studying how components of the action potential waveform modulate neurotransmission. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/41744/

Chicago Manual of Style (16th Edition):

Clarke, Stephen G., 1988-. “The ups and downs of electrical activity in the brain: studying how components of the action potential waveform modulate neurotransmission.” 2013. Masters Thesis, Rutgers University. Accessed July 11, 2020. https://rucore.libraries.rutgers.edu/rutgers-lib/41744/.

MLA Handbook (7th Edition):

Clarke, Stephen G., 1988-. “The ups and downs of electrical activity in the brain: studying how components of the action potential waveform modulate neurotransmission.” 2013. Web. 11 Jul 2020.

Vancouver:

Clarke, Stephen G. 1. The ups and downs of electrical activity in the brain: studying how components of the action potential waveform modulate neurotransmission. [Internet] [Masters thesis]. Rutgers University; 2013. [cited 2020 Jul 11]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/41744/.

Council of Science Editors:

Clarke, Stephen G. 1. The ups and downs of electrical activity in the brain: studying how components of the action potential waveform modulate neurotransmission. [Masters Thesis]. Rutgers University; 2013. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/41744/


Rutgers University

2. Rodriguez, Ana R., 1986-. The role of cypin in regulating synaptic content and transmission.

Degree: PhD, Biomedical Engineering, 2016, Rutgers University

Proper synaptic transmission is essential for normal brain function and requires the precise spatial and functional assembly of molecular signal transduction machinery at synaptic sites and the correct morphology of dendrites and their branches. Defects in synaptogenesis and dendritogenesis are implicated in neurological and neurodevelopmental disorders. Cypin (cytosolic PSD-95 interactor) is a core regulator of dendrite branching and decreases the synaptic clustering of the scaffolding protein PSD-95 in rat hippocampal neurons. This dissertation will explore the functional implications of altering cypin levels on PSD-95 protein and synaptic function. We show that overexpression of cypin decreases synaptic PSD-95 protein levels, increases total PSD-95 protein levels, and increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). We used microelectrode arrays to assess neuronal network dynamics after overexpression of cypin and uncovered changes in spiking variability that were not evident from the study of global network activity. The spike count variability of networks that overexpress cypin increases over time, and this variability is dependent on baseline activity levels. Moreover, attenuation of AMPAR-mediated synaptic transmission with the AMPAR antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) shows that cypin overexpression results in a decrease in functional AMPARs, potentially interfering with synaptic upscaling. Interestingly, we found that the alterations in synaptic transmission with overexpression of cypin are independent of cypin binding to PSD-95, whereas cypin-mediated changes in PSD-95 expression depend on cypin binding to PSD-95. Finally, we show that cypin interacts with the β7 subunit of the proteasome and interferes with its chymotryptic-like activity. Cypin overexpression results in increased ubiquitination of PSD-95, consistent with the observed increase in total PSD-95 levels. Taken together, our results suggest a proteasome-mediated role for cypin in the redistribution of PSD-95, and potentially, remodeling of the postsynaptic density associated with synaptic plasticity.

Advisors/Committee Members: Firestein, Bonnie L (chair), Paradiso, Kenneth (internal member), Pang, Zhiping P (internal member), Yarmush, Martin l (internal member), Meaney, David F (outside member), Madura, Kiran (outside member).

Subjects/Keywords: Synapses

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Rodriguez, Ana R., 1. (2016). The role of cypin in regulating synaptic content and transmission. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/51451/

Chicago Manual of Style (16th Edition):

Rodriguez, Ana R., 1986-. “The role of cypin in regulating synaptic content and transmission.” 2016. Doctoral Dissertation, Rutgers University. Accessed July 11, 2020. https://rucore.libraries.rutgers.edu/rutgers-lib/51451/.

MLA Handbook (7th Edition):

Rodriguez, Ana R., 1986-. “The role of cypin in regulating synaptic content and transmission.” 2016. Web. 11 Jul 2020.

Vancouver:

Rodriguez, Ana R. 1. The role of cypin in regulating synaptic content and transmission. [Internet] [Doctoral dissertation]. Rutgers University; 2016. [cited 2020 Jul 11]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51451/.

Council of Science Editors:

Rodriguez, Ana R. 1. The role of cypin in regulating synaptic content and transmission. [Doctoral Dissertation]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/51451/

3. Scarnati, Matthew Steven, 1986-. Evidence for presynaptic protein at the calyx of held nerve terminal.

Degree: PhD, Neuroscience, 2018, Rutgers University

Presynaptic activity requires the localization and maintenance of thousands of proteins that are typically thought to be synthesized in the soma and transported to nerve terminals. However, local protein synthesis occurs at dendritic locations and local presynaptic protein synthesis has recently been shown to occur in an inhibitory neuron in the brain, but the small size of most nerve terminals complicates further studies. Here, we study presynaptic protein synthesis at the calyx of Held nerve terminal, located in the mammalian brain. The size of this terminal, its long axon, and high firing frequency make it an ideal choice to study presynaptic protein synthesis. We show a major ribosomal component, 5.8S ribosomal RNA is present in this presynaptic nerve terminal. To verify the presence of functional presynaptic ribosomes, we used the surface sensing of translation (SUnSET) technique. This produced well-defined fluorescent signals in presynaptic terminals and postsynaptic cell bodies, and the fluorescent signal was eliminated by inhibiting protein synthesis. To determine the effects on synaptic transmission, we measured electrical activity. After inhibiting translation, the initial frequency of spontaneous events increased by ~2-fold but the amplitude was unaffected, indicating a presynaptic mechanism. In addition, we find that evoked responses show less depression during high frequency firing (≥ 100 Hz). The reduction in depression is not consistent with effects on desensitization but is well explained by presynaptic changes in neurotransmitter release. These findings further indicate that presynaptic protein synthesis occurs, that it can affect spontaneous and evoked release of neurotransmitter, and it affects neurotransmitter release at high firing frequencies.

Advisors/Committee Members: Paradiso, Kenneth (chair), Firestein, Bonnie (internal member), Plummer, Mark (internal member), Pang, Zhiping (internal member), Hengst, Ulrich (outside member), School of Graduate Studies.

Subjects/Keywords: Electrophysiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Scarnati, Matthew Steven, 1. (2018). Evidence for presynaptic protein at the calyx of held nerve terminal. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/56114/

Chicago Manual of Style (16th Edition):

Scarnati, Matthew Steven, 1986-. “Evidence for presynaptic protein at the calyx of held nerve terminal.” 2018. Doctoral Dissertation, Rutgers University. Accessed July 11, 2020. https://rucore.libraries.rutgers.edu/rutgers-lib/56114/.

MLA Handbook (7th Edition):

Scarnati, Matthew Steven, 1986-. “Evidence for presynaptic protein at the calyx of held nerve terminal.” 2018. Web. 11 Jul 2020.

Vancouver:

Scarnati, Matthew Steven 1. Evidence for presynaptic protein at the calyx of held nerve terminal. [Internet] [Doctoral dissertation]. Rutgers University; 2018. [cited 2020 Jul 11]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/56114/.

Council of Science Editors:

Scarnati, Matthew Steven 1. Evidence for presynaptic protein at the calyx of held nerve terminal. [Doctoral Dissertation]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/56114/

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