The overall goal of this proposal is to test systematically complementary hypotheses about the physiological function of decreased conductance depolarizing potentials in the nervous system. One hypothesis is that decreased conductance depolarizing potentials (DCDPs) are used as a general integrative and modulatory mechanism to enhance and integrate related behavioral actions by coordinately increasing the excitability and synaptic efficacy of sensory, motor, and interneuronal elements in neural circuits underlying synergistic responses. A related hypothesis is that DCDPs, through their effects on major cellular regulators such as cyclic nucleotides and Ca++, play an important role in the generation of long-lasting neuronal modifications underlying associative and nonassociative learning. These hypotheses will be tested by examining the cellular changes accompanying the elicitation and modulation of a coordinated ensemble of defensive responses in the mollusc Aplysia by stimulation of its tail. Each response - tail withdrawal, gill withdrawal, inking, opaline release, and respiratory pumping - involves circuits in which major sensory, motor, and interneurons have been identified. Using electrophysiological and pharmacological techniques we will determine the loci in the circuits where DCDPs operate, the conditions under which they are triggered, and the contribution they make to the functional properties of the cells. In selected cells (the tail sensory neurons and ink motoneurons) presenting perticular advantages for detailed analysis, we will use voltage clamp, computer simulation, and biochemical techniques to examine the biophysical and biochemical mechanisms by which the DCDPs are produced and, in addition, systematically analyze the mechanisms by which DCDPa can be altered by paired spike activity in the cell and thus contribute to associative modifications that may play a role in learning. These analyses may lead not only to a greater understanding of the cellular mechanisms underlying neural integration, arousal and learning but may also lead to a refinement of techniques which may then be more readily applied to the analysis of behavioral control, modifiability and abnormalities in more complex organisms, including man.
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