The long-term objective of the proposed research is to identify cellular mechanisms underlying associative learning and to relate these mechanisms to general principles of information processing by sensory systems. Building on the recent demonstration of activity-dependent associative plasticity in individual sensory neurons mediating afferent input for the tail withdrawal reflex in Aplysia, the proposed experiments will test the hypothesis that this associative plasticity is a mechanism for classical conditioning. Initially differential classical conditioning of tail withdrawal will be examined in a semi-intact preparation in which behavioral and cellular alterations in identified neurons within the reflex circuit can be measured simultaneously. An analog of the conditioning process will then be applied to the isolated sensory cell soma by pairing intracellular stimulation with bath application of the presumed neuromodulator mediating the unconditioned effects. Specific hypotheses concerning the interaction of lateral inhibition with cellular mechanisms of associative plasticity will be tested in an attempt to identify sensory processes that may contribute to complex features of associative learing. By precisely defining conditioning and test stimuli in the simi-intact preparation and relating the effects of conditioning with these stimuli to the details of cellular associations measured under analogous conditions in the isolated soma, quantitative models of the functional interactions underlying associative processing in this sensory system will be developed. If basic principles relating specific neuronal properties and patterns of organization to associative modifiability emerge, these principles will be tested in collaborative studies on a suitable vertebrate preparation. Since learning is one of the fundamental capabilities of most if not all nervous systems, these studies may shed light on general mechanisms involved in both the normal function and some of the dysfunctions of the human brain.
