The flexible cardiovascular adaptation of mammals suggests a mechanism that optimizes regulation in health and compensates for disease. Recently neural plasticity has been implicated in the long-term regulation of the the vestibular-ocular reflex (VOR); the putative mechanism, which strengthens or weakens efferent paths dependent upon their prior adaptive value, resembles what behaviorists call instrumental learning (IL). IL could have a similar role in long-term cardiovascular regulation; however, the VOR is a purely somatic system, and IL has never been convincingly demonstrated to directly modify autonomic nervous system mediated responses. Because Il is known to control many different skeletal responses, and skeletal movement influences the viscera, any convincing demonstration of autonomic IL (ANS-IL) must categorically exclude such skeletal influence. Pharmacological neuromuscular block (NMB) eliminates the effects of actual skeletal movements on the cardiovascular system, but does not exclude certain types of CNS mediated somatic learning; thus, a comprehensive dialysis of the mechanism of a learned change in cardiovascular regulation must include, in addition to NMB, measurement of the central skeletal outflow to the paralyzed muscles. In the rat long-term highly specific NMB can be achieved with alpha-Bungarotoxin. In the proposed experiments the physiological and CNS competence of a chronic NMB rat will be verified by demonstrating it capable of discriminative classical conditioning of autonomic and skeletal responses and IL of Tibial nerve activity; then, vasomotor-IL will be attempted while continuing to record from the Tibial nerve. The overall goal of this proposal is a differential test of the following hypothesis: When all skeletal mediation is eliminated, (a) tonic vasomotor activity can be modified by repeated periodic application of a brief response contingent stimulus; (b) the phase relationship between the stimulus and spontaneous vasomotor fluctuations will determine whether constriction or dilatation is produced and (c) the recorded activity of adjacent skeletal nerve will not be similarly affected by the procedure. Demonstration of ANS-IL, without correlated changes of skeletal nerve activity, will indicate that IL could have a role in long-term regulation of cardiovascular function. Because of the demonstration of other types of learning in the same preparation, failure to find evidence of ANS-IL will be convincing evidence against the hypothesis.
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