The long-term goal of this proposal is to determine, at the cellular level, how different extrinsic modulatory inputs select distinct motor patterns from multifunctional neural networks that underlie behavior. In all animals, neuromodulation enables single motor circuits to produce many different activity patterns, thereby producing distinct behaviors. The multifunctional character of such networks derives largely from the actions of modulatory transmitters which alter the cellular and synaptic properties of neurons. These substances are released by sensory, humoral and projection neurons to influence these networks. Thus far, little is known about how specific extrinsic modulatory pathwaysselect a particular motor pattern from a multifunctional network. This issue will be addressed using a well-defined model system, the isolated crabstomatogastric nervous system, in which all of the relevant neurons, synapses and membrane properties can be identified and manipulated. Specifically, (1) the distinct chewing motor pattern triggered by a newly identified extrinsic modulatory pathway will be characterized and compared with the patterns elicited by two previously studied sensory pathways. (2) This will include identifying the intervening projection neurons that mediate this action, including the underlying cellular and synaptic mechanisms. This will help establish a new cellular-level model regarding whether distinct extrinsic inputs elicit different motor outputs from the same network by activating the same, overlapping or different sets of projection neurons. (3) The state-dependent and state- independent consequences from the overlapping or sequential activation of distinct extrinsic inputs will also be determined, as will (4) the roles played by distinct co-releasedtransmitters in these processes. 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 and less accessible mammalian nervous system. Because the same organizing principles underlie network activity in all animals, this work will also facilitate a better understanding of network dysfunction that produces aberrant or loss of behavior, such as occurs as a consequence of spinal cord injury, stroke or altered modulatory states such as after drug addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042813-08
Application #
7558298
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (07))
Program Officer
Chen, Daofen
Project Start
2002-02-01
Project End
2011-01-31
Budget Start
2009-02-01
Budget End
2011-01-31
Support Year
8
Fiscal Year
2009
Total Cost
$334,407
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
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
Blitz, Dawn M; Beenhakker, Mark P; Nusbaum, Michael P (2004) Different sensory systems share projection neurons but elicit distinct motor patterns. J Neurosci 24:11381-90

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