Neuropsychological studies have established the brain's limbic system as critically important for human learning and memory processes, and limbic system degeneration is centrally involved in the etiology of Alzheimer's and Korsakoff's disease. The highly diffuse character of degenerative change in these conditions has made difficult the discovery of links between specific forms and sites of damage on the one hand and specific mnemonic and behavioral impairments on the other. Knowledge of the specific mnemonic functions and dynamic interactions of limbic brain circuits may prove helpful to the discovery of such links. Yet, little is known of these functions. The overall objective of this project is to specify completely these functions in an animal model. Past work of this project established the critical relevance of limbic circuits in relation to discriminative avoidance learning in rabbits. Studies of the neuronal activity in the behaving animal, selective lesioning, and neurochemical manipulations have fostered substantial progress toward this specification. Of particular value has been multi-channel recording, which allows documentation of learning-related neuronal activity simultaneously in six brain areas. This approach has yielded many unprecedented findings and a theoretical working model of the dynamic interactions of the cerebral cortical and thalamic limbic structures subserving learning. Studies proposed here afford major strides toward the elaboration of a veridical model. These studies will indicate: a) how the convergence of tegmental cholinergic and mammillothalamic afferents brings about training-induced neuronal plasticity in limbic thalamus; b) the pathway whereby cue-driven auditory information that triggers the learned response accesses the sites of critical learning-relevant plasticity in limbic thalamus; c) the functional relevance of training-stage related peaks of learning-relevant plasticity in subdivisions of the anterior thalamus; d) the dynamic interactions of hippocampal with limbic cortical and thalamic circuits that govern the training-stage related peaks of plasticity and suppression of learned behavior in response to unexpected events; e) the pathways whereby learning-relevant plasticity in limbic circuits accesses the motor system to produce output of the learned behavior.
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