GRADED SYNAPTIC TRANSMISSION IN LOCAL NEURAL CIRCUITS

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The objective of the proposed research is to increase our understanding of the synaptic mechanisms used by local circuit neurons and, in particular, to study the function of graded synaptic transmission in spiking, local circuit neurons. The immediate objective is to understand the contributions of graded, spike-evoked, and neuromodulator synaptic transmission to the functioning of a small neural network, the stomatogastric ganglion of lobsters and crabs. In earlier years of this grant, the physiological properties and some of the underlying mechanisms of graded synaptic transmission were described. In the next grant period, the focus will be on anatomical aspects of neuron structure and synaptic organization, and on correlated physiological measurements of voltage spread both within a neuron and between connected cell pairs. The methods to be used include: intracellular recording and dye injection, voltage clamp, immunostaining, and confocal microscopy. Stomatogastric neurons have the serial synaptic structure, extended dendrites, and graded synaptic properties that appear to be ideally designed for regional computation. However, so far there is no evidence that they regionally compute and it is not clear how they avoid doing so. Neuromodulators can functionally rewire the synaptic connections in the stomatogastric ganglion, but we don't known where they act. Thus, information on the synaptic organization of these neurons and on their electrotonic properties is essential if we are to understand the contribution made by each neuron to the functioning of this local neural circuit. Providing that information is the objective of this proposal. These neurons are structurally similar to less accessible thalamic neurons in humans and the stomatogastric motor network serves as a model for human rhythmic motor functions, including walking and chewing. By increasing our knowledge of how this model system works, we may gain clues to what underlies common motor pathologies and to how the system can be readjusted to restore normal function.