A classical conditioning protocol applied directly to individual tail sensory neurons in Aplysia results in an associative modification of the monosynaptic connections to tail motor neurons. Sensory neurons receiving a conditioned stimulus (CS, intracellular activation of the sensory neuron) immediately before the unconditioned stimulus (US, tail shock) show significantly more synaptic facilitation than sensory neurons exposed to the US alone or to unpaired CS and US applications. An analog of the classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. These results indicate that a pairing-specific enhancement of cAMP levels may be a biochemical mechanism for associative learning. Experiments proposed here are designed to extend these analyses. Specifically, we will examine 1) whether Ca2+ serves as the signal for the induction of the associative change, 2) whether cAMP levels in the sensory neurons are increased during simple forms of learning such as sensitization and classical conditioning, 3) the contribution of spike broadening in the sensory neurons to synaptic facilitation and behavioral modifications, 4) the properties of the neural circuit elements mediating the tail withdrawal reflex and effects of the US, and 5) the coordination of synergistic defensive responses triggered by tail stimulation. The tail withdrawal reflex offers a unique opportunity to investigate the cellular and molecular basis of learning. Few systems offer all the advantages found in this preparation; a simple stereotyped behavior for which the neural circuitry is relatively well defined, a large homogeneous population of identifiable cells that are accessible for biochemical and biophysical assay, and a testable hypothesis. Continued analysis of this system promises to yield much additional information concerning the cellular mechanisms underlying associative and nonassociative learning.
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