Motor Circuit Modulation and its Regulation

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DESCRIPTION (provided by applicant): The long-term goals of this project are to understand, at the cellular level, how the central nervous system selects and generates the neuronal activity patterns underlying movement. This includes determining the flexibility inherent in motor circuits and during coordination of behaviorally-related circuits, plus determining the cellular mechanisms underlying such events. This work focuses on rhythmically active motor circuits, such as those underlying walking, breathing, and chewing. A well-defined model system, the crab stomatogastric nervous system, will be used. Previous work has shown that the same general principles underlie the generation of rhythmic motor programs in all animals. This proposal aims to extend previous work by determining the mechanisms used by identified modulatory projection neurons to alter the output of two well-defined motor circuits, the gastric mill (chewing) and pyloric (filtering of chewed food) circuits. Three hypotheses will be tested: (1) Different modulatory inputs can elicit the same neuronal activity pattern via distinct cellular mechanisms; (2) The neurons and synapses responsible for rhythm generation can be altered by projection neuron-elicited modulation; (3) Circuit regulation of projection neuron activity can determine circuit output. These studies will be done using electrophysiological and pharmacological approaches to monitor and manipulate the activity of circuit and projection neurons. A computer program called the Dynamic Clamp will be used to inject realistic versions of synaptic and ionic currents into single neurons. The stomatogastric system is one of the few biological systems in which a detailed intracellular analysis of neuronal network activity is possible and in which there is a population of identified projection neurons. Thus, the proposed studies will provide a valuable template for understanding comparable events in the numerically larger and less accessible mammalian central nervous system. It will also facilitate understanding the motor dysfunctions that occur as a result of events such as spinal cord injury and stroke.