9514619 Clark Learning and synaptic plasticity -- the modification of communication between nerve cells -- play a central role in a wide variety of cognitive and neuronal processes. Because a single neuron can make synaptic contacts with thousands of other neurons, a fundamental question is whether increases in synaptic strength are necessarily expressed cell-wide at all connections of a given neuron, or can instead be synapse- specific and so occur at only selected connections of the cell. To investigate synapse-specific facilitation, this research program utilizes a favorable simple model system, and focuses on cells known to exhibit learning-related increases in synaptic strength. Studies will first determine whether long-term (> 24 hr) as well-as short-term increases in synaptic strength can be synapse-specific. This is a critical issue, given that long-term facilitation appears to depend on changes in gene expression. The neurotransmitter serotonin will be applied selectively onto particular synapses in order to induce facilitation, and intracellular electrophysiological recordings will be used to test whether synaptic facilitation is greater at treated synapses compared with other synapses of the same cell. Second, studies will investigate underlying cellular mechanisms. These studies will provide new insights into the conceptual and mechanistic relationships between short-term and long- term memory, and illuminate key cellular and molecular steps underlying learning-related neuronal change.