This work addresses the mechanisms by which the neural networks that control behavior are modulated by neurotransmitters and neurohormones. The proposed experiments are designed to determine how the modulatory substances in the nervous system a) modify the properties of individual neurons, and b) alter the ways in which neurons interact. The rhythmically active central pattern generating circuits of the crustacean stomatogastric nervous system provides an ideal experimental preparation for this work. Anatomical techniques are used to determine which neuromodulators are colocalized in identified neurons. Electrophysiological and biophysical recording methods are used to characterize membrane and modulator currents. A new method, the dynamic clamp, will be employed to modify the intrinsic properties of individual neurons and their connections to determine their influence on circuit dynamics. The movements resulting from circuit modulation will be studied. Together these approaches will explain how behavior is produced at the cellular level. Neural oscillators and oscillatory networks contribute to sensory and motor behavior, but relatively little is understood about how oscillatory neurons and networks function, and malfunction in movement disorders and epilepsy. The proposed work addresses a number of fundamental problems related to neural oscillators. Moreover, the mechanisms by which single neurons can be recombined into several different functional circuits are studied. These studies will aid our understanding of the ways in which the modulatory environment of the brain shapes brain function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017813-18
Application #
2839284
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Leblanc, Gabrielle G
Project Start
1981-12-01
Project End
1999-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
18
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Brandeis University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Rosenbaum, Philipp; Marder, Eve (2018) Graded Transmission without Action Potentials Sustains Rhythmic Activity in Some But Not All Modulators That Activate the Same Current. J Neurosci 38:8976-8988
Nusbaum, Michael P; Blitz, Dawn M; Marder, Eve (2017) Functional consequences of neuropeptide and small-molecule co-transmission. Nat Rev Neurosci 18:389-403
Marder, Eve; Gutierrez, Gabrielle J; Nusbaum, Michael P (2017) Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms. Dev Neurobiol 77:597-609
Gjorgjieva, Julijana; Drion, Guillaume; Marder, Eve (2016) Computational implications of biophysical diversity and multiple timescales in neurons and synapses for circuit performance. Curr Opin Neurobiol 37:44-52
Marder, Eve (2015) Understanding brains: details, intuition, and big data. PLoS Biol 13:e1002147
Marder, Eve; Goeritz, Marie L; Otopalik, Adriane G (2015) Robust circuit rhythms in small circuits arise from variable circuit components and mechanisms. Curr Opin Neurobiol 31:156-63
Gutierrez, Gabrielle J; Marder, Eve (2014) Modulation of a Single Neuron Has State-Dependent Actions on Circuit Dynamics(,.) eNeuro 1:
Shruti, Sonal; Schulz, David J; Lett, Kawasi M et al. (2014) Electrical coupling and innexin expression in the stomatogastric ganglion of the crab Cancer borealis. J Neurophysiol 112:2946-58
Hamood, Albert W; Marder, Eve (2014) Animal-to-Animal Variability in Neuromodulation and Circuit Function. Cold Spring Harb Symp Quant Biol 79:21-8
Marder, Eve; O'Leary, Timothy; Shruti, Sonal (2014) Neuromodulation of circuits with variable parameters: single neurons and small circuits reveal principles of state-dependent and robust neuromodulation. Annu Rev Neurosci 37:329-46

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