The long-term objective of these experiments is to understand the organizational principles which underlie the ability of simpler nervous systems to generate and modulate behaviors. These questions will be addressed using voltage-sensitive dye recordings which allow simultaneous monitoring of action potential activity of several hundred neurons. In experiments on the Aplysia abdominal ganglion this is about half of the total number of neurons. There is now considerable evidence that nervous systems in general, and the Aplysia CNS in particular, function in a distributed manner. A large number of central neurons (approximately 1,000) are activated by a very mild and localized siphon stimulus. Evidence from C. elegans suggests that the convergence of information onto motor neurons is just as dramatic as the divergence of information from sensory neurons. Taken together, these results strongly suggest a distributed functional organization in Aplysia. The main aim of the present proposal has two parts. The first is to use a combination of optical and microelectrode recordings to provide the experimental evidence to support a qualitative understanding of the generation of the gill-withdrawal reflex. The second part is to define exactly what a distributed system means in terms of the activity and interactions of its constituent neuronal elements. In addition there are three subsidiary goals. The first is to locate the sensory neurons involved in the response to siphon touch. The second is carry out optical recordings during sensitization in an attempt to find new functional groups of neurons. The third is to determine how the response to sensory stimuli is affected by using a sensorially deprived and very reduced preparation. All of the above experiments would greatly benefit from larger optical signals. We plan efforts in two directions, first, to find better dyes and second, to explore new methods for delivering the dye to specific neuron subsets. Two laboratories have recently announced the first optical measurements of activity in human cortex. It seems highly likely that this kind of measurement will have considerable clinical utility. Improvements generated by the proposed experiments will be important in achieving that goal.
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