The intrinsic properties of neurons can be modified by changes in their electrical activity. Though much less studied than synaptic plasticity, activity-dependent modifications of intrinsic neuronal properties can have an important impact on neural network function. The proposed research is part of an ongoing study of how oscillatory and plateau properties of individual neurons affect network behavior. In previous work, neuron models with dynamically regulated conductances were constructed and shown to display interesting activity-dependent changes when perturbed, stimulated or coupled into networks. Related experimental work showed that the intrinsic properties of stomatogastric ganglion (STG) neurons in primary cell culture are dramatically modified by prolonged shifts in their patterns of activity. The STG also modifies its mode of operation, both in organ culture and in vivo, when changes in its modulatory inputs suppress activity. As part of a continuing analysis of the dynamics of oscillatory networks, these phenomena will be studied and modeled in detail. Specifically the proposed research will: l) Study the effects of activity on the intrinsic properties of single STG neurons in primary cell culture and model the dynamics of the conductance changes seen. 2) Construct two- and three-cell networks of cultured STG neurons using both artificial and naturally occurring synapses to study the impact of intrinsic plasticity on network function. Parallel modeling studies will explore this question and study the interplay between intrinsic and synaptic plasticity. 3) Study the plasticity of the full pyloric circuit of the STG in organ culture and in vivo. Dynamic regulation of conductances will be used as a tool to construct a model of the pyloric network and then to explore its development and study how perturbations in its modulatory environment induce long-term changes in its properties.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH046742-08
Application #
2392911
Study Section
Special Emphasis Panel (SRCM (03))
Project Start
1990-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
8
Fiscal Year
1997
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
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
Otopalik, Adriane G; Lane, Brian; Schulz, David J et al. (2017) Innexin expression in electrically coupled motor circuits. Neurosci Lett :
Northcutt, Adam J; Lett, Kawasi M; Garcia, Virginia B et al. (2016) Deep sequencing of transcriptomes from the nervous systems of two decapod crustaceans to characterize genes important for neural circuit function and modulation. BMC Genomics 17:868
Lane, Brian J; Samarth, Pranit; Ransdell, Joseph L et al. (2016) Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network. Elife 5:
O'Leary, Timothy; Sutton, Alexander C; Marder, Eve (2015) Computational models in the age of large datasets. Curr Opin Neurobiol 32:87-94
Christie, Andrew E; Chi, Megan; Lameyer, Tess J et al. (2015) Neuropeptidergic Signaling in the American Lobster Homarus americanus: New Insights from High-Throughput Nucleotide Sequencing. PLoS One 10:e0145964
Marder, Eve (2015) Understanding brains: details, intuition, and big data. PLoS Biol 13:e1002147
Hamood, Albert W; Marder, Eve (2015) Consequences of acute and long-term removal of neuromodulatory input on the episodic gastric rhythm of the crab Cancer borealis. J Neurophysiol 114:1677-92
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
Brookings, Ted; Goeritz, Marie L; Marder, Eve (2014) Automatic parameter estimation of multicompartmental neuron models via minimization of trace error with control adjustment. J Neurophysiol 112:2332-48

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