This work addresses the mechanisms by which the neural networks that control behavior are modulated by modulatory neurons and the substances they contain. By altering the intrinsic membrane properties and synaptic strengths within a network, modulatory substances functionally """"""""construct"""""""" or """"""""specify"""""""" a circuit active during a specific behavior, from the matrix of possibilities defined by the anatomical and biophysical properties of the individual neurons and their connections. In the proposed work, the rhythmic central pattern generating networks in the crustacean stomatogastric nervous system will be used. The small number of neurons in these preparations allows detailed mechanisms of cellular and circuit modulation to be investigated. Electrophysiological and biophysical methods will be used to study the cellular targets of six modulators that converge onto the same membrane current. This work has implications for understanding how neurons that use multiple cotransmitters elicit specific behaviors. The effects of neuromodulatory substances on the encoding of sensory information will be investigated using electrophysiological methods. This work will provide a better understanding of the mechanisms by which sensory information is modified by behavioral state. Anatomical and electrophysiological experiments will determine if differences between embryonic, larval and adult motor patterns are attributable to different neuromodulatory environments, and/or circuit modifications. It is commonly thought that perturbations in the modulatory environment of the brain accompany or cause some mental illnesses. The proposed work will enable a better understanding of how stability in functional neural circuits is maintained, and how these processes may be disrupted in illness.
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