INTRINSIC NEUROMODULATION OF A SMALL NEURONAL NETWORK

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Neuronal networks are often multifunctional, that is, a single group of cells with anatomically defined synaptic connections can be reconfigured to produce different outputs. A major question that needs to be addressed is, how does this reconfiguration occur? Several studies have shown that circuit reconfiguration can be caused by extrinsic neuromodulatory inputs that alter neuronal properties and synaptic strengths. Alternatively, circuits can be self-reconfiguring, rearranging themselves based on their own activity pattern. Recent evidence suggests this may arise as a result of neuromodulatory actions of neurons intrinsic to the network. The purpose of this study is to examine the role of "intrinsic neuromodulation" in circuit reconfiguration and rhythmic pattern generation. There is a network of neurons in the marine mollusc Tritonia that is capable of changing itself from a circuit that mediates a withdrawal reflex to one that produces a rhythmic escape swim behavior. Two cell types in the network evoke neuromodulatory effects on other cells in the circuit (one cell type is serotonergic, the other peptidergic). Since these cells are integral parts of the pattern generating circuit, they are activated during every swim episode. Thus, the circuit appears to modulate itself every time that it is activated and throughout its performance of the behavior. The specific aims of this project are to I) identify the cellular and synaptic loci of intrinsic neuromodulation in the Tritonia swim circuit; II) determine the role of serotonin in producing some of these neuromodulatory effects; and Ill) study the role of intrinsic neuromodulation in circuit reconfiguration and pattern generation by adding the modulation to an existing computer simulation of the circuit. Studying this small neural network will provide more insights into the mechanisms of intrinsic neuromodulation, and will increase our understanding of the functional significance of this little-recognized form of nervous system plasticity.