The long-term objective is to analyze the cellular mechanisms underlying two important capabilities of the nervous system: (1) the ability to associate a given stimulus with a novel motor response (stimulus-response or S-R learning), and (2) long-term sensory modifiability. This objective requires the development of preparations, involving well-defined behavioral alterations and identified neuronal networks, that permit direct analysis of physiological mechanisms. Building on preliminary studies using the siphon, tail, head, and parapodia of the marine gastropod, Aplysia, intact and semi-intact preparations will be developed that show the acquisition of novel siphon responses after pairing parapodial stimulation with head or tail stimulation. Electrophysiological correlates of this S-R conditioning will be examined in identified siphon motor neurons and interneurons. Two hypotheses for the development of novel S-R connections will be tested using intracellular recording, voltage clamp, and quantal analysis techniques. Long-term sensory memory will be investigated in the central and peripheral processes of parapodial sensory neurons, which offer special advantages for sensory analysis. The general hypothesis that associative information storage in sensory systems makes use of mechanisms evolved for sensory compensation after injury will be tested. The contribution of a specific cellular associative mechanism - activity-dependent extrinsic modulation (ADEM) - to sensory modifiability will be tested. Several potential ADEM-related enhancements of signaling effectiveness produced by associative conditioning and by injury of the receptive field will be examined: synaptic facilitation, increased central and/or peripheral excitability, and sprouting of peripheral and/or central processes. These studies should provide basic information on general mechanisms of learning, sensory compensation, and neuronal regeneration that may eventually contribute to an understanding of normal and abnormal physiological plasticity within the human nervous system.
