The proposed research program will investigate the neurobiological bases of learning and memory in mammalian species. A considerable body of evidence indicates that: 1) the """"""""paradigmatic"""""""" approach (i.e., the use of awake, intact, non-drugged animals learning within traditional conditioning paradigms) is an effective strategy to use in researching this problem, 2) the limbic system (i.e., the hippocampus and related structures) is centrally involved in learning/memory processes and limbic neurons change their physiological response (i.e., exhibit neural plasticity) during learning, 3) the majority of hippocampal efferents are cortically directed to subicular and cingulate cortices, making the hippo-campal-subicular-cingulate circuit an important component of the limbic system, 4) successful learning of discrimination/reversal problems uniquely requires normal functioning of limbic system processes, and 5) anatomical/physiological identification of neurons that are modified during the course of learning is a critical step in the determination of cellular mechanisms of learning. As a result of these considerations, the proposed research will utilize electrophysiological techniques to extracellularly record from single neurons of the hippocampus, subiculum and cingulate cortex during discrimination/reversal classical conditioning in the intact rabbit. The particular behavioral paradigm to be used is known to induce changes in limbic neurons and physiological identification will be attempted on all recorded cells to determine their anatomical type and their relationship with respect to limbic cortical synaptic organization. Axonal transport neuroanatomical methods will be used to: 1) describe the interconnections between hippocampus, subiculum and cingulate cortex, 2) document the course of fiber bundles mediating afferent and efferent connections for use in physiological identification procedures, and 3) interrelate neuronal plasticity recorded from these three limbic cortical regions during the course of conditioning.
