Studies of human neuropathology have implicated the limbic system in the mediation of learning and memory processes. In accord with this result, our studies of unit activity in behaving animals have shown differentiation of neuronal responses to stimuli with varied associative significance. These effects occur in a triad of reciprocally interconnected limbic structures (the cingulate cortex, anteroventral thalamic nucleus [AVN], and hippocampal formation). Neurons in the deep cingulate cortical layers manifest discriminative firing in the early training stages, but the AVN and the superficial layers do not discriminate until discriminative behavior is well established. Similar relationships hold in the relative prefrontal corticothalamic system, but in this instance, the development of discriminative firing is accelerated, relative to the limbic triad. These results form the basis of a theory in which it is posited that the function of limbic forebrain in learning processes is the encoding and """"""""extraction"""""""" of que significance. The sequential character of the developing differential responses provided the rationale for the model's hypotheses about the causal relationships among the involved structures. Recent tests supported the model's hypotheses that the late discriminative code in the upper cortical layers originates in the AVN, and that the hippocampal formation (subiculum) exerts a tonic suppressive influence over neuronal firing in the cingulate cortex. This suppressive control, predicted by the model, provides a mechanisms to account for the behavioral hyperreactivity shown by animals with hippocampal damage. A major breakthrough has been the realization that the structures of the limbic triad produce an """"""""automatic"""""""" neural code relevant to the performance of well learned behavior, but not to its original acquisition. The analogous code in the prefrontal system is the """"""""leading edge"""""""" code subserving acquisition. Thus our studies identify separate neurobiological substrates for original discriminative acquisition, and for the maintenance of well learned behavior. Most importantly, the recent work indicates that selective removal of afferents yields selective neuronal effects in the recipient structures, and selective behavioral deficits. This general result supports the efficacy of our strategy for the functional analysis of interacting brain systems in relation to ongoing behavior. The proposed studies continue the analytic strategy by investigating the contributions to the significance coding process in the limbic triad made by afferents from the prefrontal system, the noradrenergic and basal forebrain cholinergic projections, the mammillothalamic projection, and possible influences of the pontine reticular formation.
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