The long-term goal of this proposal is to determine, at the cellular level, how distinct motor patterns are elicited by different sensory and descending inputs to multifunctional neural networks that underlie behavior. Previous work in many model systems showed that one common principle underlying the neural basis of behavior is that single neural networks produce many different neural activity patterns, thereby producing distinct behaviors. The multifunctional character of such networks derives from the actions of modulatory neurotransmitters which alter the cellular and synaptic properties of the network neurons. Thus far, little is known regarding how the nervous system selects which activity pattern should be elicited by a given network. In this context, identified projection and sensory neurons will be studied to determine how this selection process is orchestrated. This will include a determination of the roles played by the (a) co-release of neurotransmitters, (b) activity-dependent regulation of transmitter release, and (c) activation of distinct sets of projection neurons. This proposal aims to take advantage of a well-defined model system, the stomatogastric nervous system of the crab, to elucidate the cellular mechanisms whereby multitransmitter modulatory neurons elicit distinct outputs from well-defined networks. Because neural networks are basic building blocks underlying all behaviors, and many of the same organizing principles pertain to network activity in all animals, this work aims to better elucidate how the nervous system generates behavior. This will facilitate a better understanding of network dysfunction that produces aberrant or loss of behavior, such as occurs after spinal cord injury or stroke. Because this research will study the modulation of network function, it will also contribute to general principles that must be understood to address aberrant behaviors occurring during altered states, for example as occurs as a result of drug addiction. This proposal aims to combine cellular neurophysiological, pharmacological and anatomical approaches to elucidate general principles about motor pattern selection from multifunctional networks. This will guide comparable studies in the more complex, mammalian nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042813-03
Application #
6699356
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Chen, Daofen
Project Start
2002-02-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
3
Fiscal Year
2004
Total Cost
$330,105
Indirect Cost
Name
University of Pennsylvania
Department
Neurosciences
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Blitz, Dawn M; Nusbaum, Michael P (2011) Neural circuit flexibility in a small sensorimotor system. Curr Opin Neurobiol 21:544-52
White, Rachel S; Nusbaum, Michael P (2011) The same core rhythm generator underlies different rhythmic motor patterns. J Neurosci 31:11484-94
DeLong, Nicholas D; Beenhakker, Mark P; Nusbaum, Michael P (2009) Presynaptic inhibition selectively weakens peptidergic cotransmission in a small motor system. J Neurophysiol 102:3492-504
Blitz, Dawn M; Nusbaum, Michael P (2008) State-dependent presynaptic inhibition regulates central pattern generator feedback to descending inputs. J Neurosci 28:9564-74
Blitz, Dawn M; White, Rachel S; Saideman, Shari R et al. (2008) A newly identified extrinsic input triggers a distinct gastric mill rhythm via activation of modulatory projection neurons. J Exp Biol 211:1000-11
Beenhakker, Mark P; Kirby, Matthew S; Nusbaum, Michael P (2007) Mechanosensory gating of proprioceptor input to modulatory projection neurons. J Neurosci 27:14308-16
Kirby, Matthew S; Nusbaum, Michael P (2007) Central nervous system projections to and from the commissural ganglion of the crab Cancer borealis. Cell Tissue Res 328:625-37
Beenhakker, Mark P; DeLong, Nicholas D; Saideman, Shari R et al. (2005) Proprioceptor regulation of motor circuit activity by presynaptic inhibition of a modulatory projection neuron. J Neurosci 25:8794-806
Beenhakker, Mark P; Nusbaum, Michael P (2004) Mechanosensory activation of a motor circuit by coactivation of two projection neurons. J Neurosci 24:6741-50
Christie, Andrew E; Stein, Wolfgang; Quinlan, John E et al. (2004) Actions of a histaminergic/peptidergic projection neuron on rhythmic motor patterns in the stomatogastric nervous system of the crab Cancer borealis. J Comp Neurol 469:153-69

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