The long-range goal of this work is to understand, at the cellular level, how the central nervous system selects and generates the neuronal activity patterns underlying coordinated movements. This includes understanding how the activity of distinct but behaviorally-related neuronal circuits is coordinated to generate complex behavior. This work focusses on rhythmic motor circuits, such as those underlying locomotion, respiration and the chewing of food. A well-defined model system, the stomatogastric nervous system of the crab will be used for this purpose. Previous work has documented that the same organizing principals underlie the generation of individual rhythmic motor programs in all invertebrates and vertebrates. Relatively simple model systems are more accessible than the comparable systems in the vertebrate spinal cord and brainstem. Thus, they are more useful for a cellular analysis of neuronal circuits. This proposal aims to extend previous studies by performing a cellular analysis of how the activity of behaviorally- related neuronal circuits is coordinated. The working hypotheses is that the coordination between related, rhythmically active neuronal circuits is state-dependent. The working hypothesis is that the coordination between related, rhythmically active neuronal circuits is state- dependent. This hypothesis will be tested by examining the coordination between different versions of the motor patterns produced by the gastric mill and pyloric neural circuits in the crab stomatogastric ganglion. The following four specific aims will be examined. First: inter-circuit interactions are different between distinct forms of the gastric mill and pyloric motor programs. Second: there are distinct cellular mechanisms subserving these different inter-circuit interactions. Third: the interactions, and their functional consequences, between these two circuits are modified by locally-released and circulating neuromodulators. Fourth: patterned feedback from these two circuits onto the projection neurons that influence them enables these circuits to regulate and coordinate the activity of these projection neurons.
These aims will be investigated using a cellular electrophysiological approach, combined with a computer program called the Dynamic Clamp that enables the injection of an artificial synapse, in situ, into any neuron after the neuronally-elicited synaptic input is removed. The electrophysiological experiments will include four simultaneous intracellular recordings plus multiple extracellular recordings. This enables a comprehensive recording of all circuit activity, and the ability to manipulate all members of the studied circuits. Despite the fact that most complex behaviors, in all animals, result from interactions between distinct motor circuits, there are no existing physiological models of motor circuit coordination at the cellular level. Consequently, these proposed studies will provide a useful template for both experimental and computational models of motor pattern coordination in the numerically larger and technically less accessible vertebrate central nervous system.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1 (01))
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Heetderks, William J
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University of Pennsylvania
Schools of Medicine
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