This proposal aims to understand the role that short-term synaptic dynamics, such as depression and facilitation, play in the generation and coordination of oscillations in the nervous system. Synaptic interactions are key to the generation of temporal dynamics and are present in all synapses, but only recently have been studied in the context of generation and patterning of oscillations. In an oscillatory network, such short-term dynamics provide a mechanism that allows synapses to adjust their strength as a function of frequency;the synapses, in turn, shape the output of the network. This recursive relationship underlies the formidable complexity of these networks. Small neuronal networks are amenable to studying such complexities. We investigate the cellular and synaptic mechanisms underlying oscillations in the crustacean pyloric network, a model system for studying rhythmic motor pattern generation. Using a combination of electrophysiology and computational modeling techniques, we examine how distinct mechanisms of synaptic release interact to produce synaptic output.
Our aim i s to understand how the effects of frequency on synaptic strength give rise to new emergent network properties. There is overwhelming evidence that network activity is shaped not only by synaptic dynamics, but also by extrinsic neuromodulation, enabling networks to produce multiple functional outputs. Furthermore, synaptic dynamics are also altered by neuromodulators, thus leading to new patterns of network activity. We explore how neuromodulation affects short-term synaptic dynamics and how these effects reshape the network output. Characterizing the effects of neuromodulatory substances on synaptic dynamics may elucidate the actions of these substances in generating network oscillations such as during transitions between sleep and arousal states. Model networks in invertebrates have been used for decades to extract principles that were later shown to apply in mammalian networks. General principles obtained from studying the functions of synaptic dynamics in the generation and coordination of pyloric oscillations may potentially apply to other oscillatory networks that show activity-dependent changes in synaptic efficacy. Understanding these cellular and synaptic mechanisms provides important insight into the generation of self-organized oscillations of the brain, such as the multiple rhythms observed during sleep cycles or in structures involved in learning and memory formation and often affected in pathological conditions including epilepsy, depression and schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060605-09
Application #
7663967
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Glanzman, Dennis L
Project Start
1999-12-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
9
Fiscal Year
2009
Total Cost
$229,038
Indirect Cost
Name
Rutgers University
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
075162990
City
Newark
State
NJ
Country
United States
Zip Code
07102
Li, Xinping; Bucher, Dirk; Nadim, Farzan (2018) Distinct Co-Modulation Rules of Synapses and Voltage-Gated Currents Coordinate Interactions of Multiple Neuromodulators. J Neurosci 38:8549-8562
Anwar, Haroon; Li, Xinping; Bucher, Dirk et al. (2017) Functional roles of short-term synaptic plasticity with an emphasis on inhibition. Curr Opin Neurobiol 43:71-78
Golowasch, Jorge; Bose, Amitabha; Guan, Yinzheng et al. (2017) A balance of outward and linear inward ionic currents is required for generation of slow-wave oscillations. J Neurophysiol 118:1092-1104
Zhang, Yang; Bucher, Dirk; Nadim, Farzan (2017) Ionic mechanisms underlying history-dependence of conduction delay in an unmyelinated axon. Elife 6:
Fox, David M; Tseng, Hua-An; Smolinski, Tomasz G et al. (2017) Mechanisms of generation of membrane potential resonance in a neuron with multiple resonant ionic currents. PLoS Comput Biol 13:e1005565
Chen, Yinbo; Li, Xinping; Rotstein, Horacio G et al. (2016) Membrane potential resonance frequency directly influences network frequency through electrical coupling. J Neurophysiol 116:1554-1563
Anwar, Haroon (2016) Capturing intracellular Ca2+dynamics in computational models of neurodegenerative diseases. Drug Discov Today Dis Models 19:37-42
Daur, Nelly; Nadim, Farzan; Bucher, Dirk (2016) The complexity of small circuits: the stomatogastric nervous system. Curr Opin Neurobiol 41:1-7
Mouser, Christina; Bose, Amitabha; Nadim, Farzan (2016) The role of electrical coupling in generating and modulating oscillations in a neuronal network. Math Biosci 278:11-21
Kintos, Nickolas; Nusbaum, Michael P; Nadim, Farzan (2016) Convergent neuromodulation onto a network neuron can have divergent effects at the network level. J Comput Neurosci 40:113-35

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