The overall objective of the proposed research is to provide insights into one of the most fundamental problems in the neurosciences - the physiological basis of learning and memory. The project has three specific aims. The first aim analyzes mechanisms underlying alterations in both the biochemical and biophysical properties of individual neurons and the strength of synaptic connections between neurons that are associated with a simple form of learning known as sensitization. It examines the complex interactions between the activation of second messenger systems and the modulation of membrane currents and the facilitation of transmitter release. Specific objectives of this first aim include: 1) To determine whether the delayed potassium current is modulated by sensitizing stimuli and how the time course of this modulation compares to that of sensitization and synaptic facilitation; 2) To determine the second messenger(s) and protein kinase(s) that modulate the current; 3) To examine the time-dependence and interactions among second messengers in early and intermediate-term synaptic facilitation; and 4) To examine whether the sodium current is regulated by modulatory transmitters. The second aim addresses a fundamental issue in the cellular analysis of memory: the relationships between the cellular loci and the mechanisms of short- and long-lasting memories. Specific objectives of this second aim include: 1) To establish the electrophysiological correlates of long-term information storage following sensitization training and to compare these changes to those induced by transiently elevated levels of the second messenger, cAMP; 2) To determine the contribution of gene transcription and translation to the electrophysiological changes induced by sensitization training; and 3) To determine whether there are multiple stages of long-term memory. The final aim of the proposal examines distributed representations of learning and memory and seeks to determine whether mechanisms for induction, maintenance and expression are shared among different sites. Specific objectives of this third aim include: 1) To examine and analyze short-term plastic properties of interneurons and modulatory neurons; 2) To determine whether interneurons are involved in the storage of memory for long-term sensitization; and 3) To examine the ionic mechanisms and possible second messengers involved in modulation of the properties of interneurons. Learning and memory are unquestionably important components of biological intelligence and manifest themselves in aspects of cognitive function, language and motor control. Knowledge of the fundamental mechanisms underlying learning and memory are necessary to understand these complex functions of the brain. The application of this knowledge may lead to an understanding and treatment of learning disabilities.