OPTICAL STUDIES OF NEURON ACTIVITY AND ORGANIZATION

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DESCRIPTION (Adapted from applicant's abstract): An understanding of how a nervous system generates a behavior requires information about the brain at several levels. The proposed experiments are aimed at addressing relatively unexplored questions concerning three aspects of how the gill withdrawal reflex is generated by the Aplysia abdominal ganglion. The proposed experiments make use of several advantages of the relatively simple nervous system. One striking feature of the gill withdrawal reflex is its plasticity. Both habituation and sensitization have been demonstrated in many laboratories; now there is evidence for the presence of NMDA receptor dependent LTP. The role that the sensory neuron axon terminals play in this behavioral plasticity will be investigated. Voltage sensitive dyes and calcium indicator dyes will be used to investigate the propagation of the action potential into the nerve terminal and the subsequent calcium entry to determine the role of these processes in explaining the behavioral plasticity. Twenty-three groups of interneurons are thought to participate in the gill withdrawal reflex. Thus, far the quantitative contribution of only one of these is known. For each interneuron group, the cell(s) will be hyperpolarized and/or killed to determine the effect of removal on the activity of other neurons and on the behavior. The cells will be driven to determine the number and location of follower neurons. Several hundred neurons in the abdominal ganglion respond to a light touch to the siphon skin using a rather reduced in vitro preparation comprised of siphon skin, abdominal ganglion, and gill. Does a similar number of neurons respond with similar spike patterns in the intact animal? Is the response altered by habituation and sensitization in the same way? The optical methods we have developed have been extensively used in two clinical areas. First, to follow the propagation of the action potential in the heart to study arrhythmias. Second, to study the origins and spread of epileptic activity in intact brains and in brain slices. More recently, these methods have been used in a third area, the determination of the location of cortical speech areas in patients undergoing surgery for epilepsy.