Mechanisms Mediating Neural Network Modulation

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DESCRIPTION:(provided by applicant) 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.