CONDITIONED RESPONSE TIMING AND INTEGRATION

描述（改编自申请人摘要）：本文的中心问题

DESCRIPTION (Adapted from applicant's abstract): A central question in the neurobiology of learning and memory is the extent to which single neurons integrate real-time information from multiple sources. Predictions of Sutton and Barto's 1990 Time Derivative (TD) model of Pavlovian learning will be tested in behavioral and single-unit recording studies of the cerebellum, using the conditioned rabbit eyeblink response as a model system. Because its parametric features and neural substrates have been well characterized, classical eyeblink conditioning in humans and other species has been applied to several health related problem-areas, including aging, brain function, development, drug abuse, and toxicology. A growing body of evidence from a variety of methodologies suggests that the cerebellum is essential for learning and performance of conditioned eyeblink responses. The aim is to determine whether the firing patterns of single neurons in the cerebellum are capable of representing the timing and amplitude of classically conditioned eyeblink responses among rabbits trained in paradigms requiring real-time integration of information about the timing and likelihood of the unconditioned stimuli (US). Conditioned responses typically anticipate the timing of the US, but the peak amplitude of the response corresponds to the temporal locus of the US. Training with two conditioned stimulus (CS)-US intervals, which vary randomly from one training trial to the next, a paradigm called temporal uncertainty, produces bimodal response topographies. Because they reflect two expectations of US timing, such bimodal responses express temporal integration. Other paradigms that require this sort of processing include blocking, second-order conditioning, conditioned inhibition, and others. The research plan has three components. (1) behavioral tests of the TD model regarding conditioned response topography; (2) micro-electrode recording from single neurons of the cerebellum after animals have achieved stable (asymptotic) modes of responding; (3) development and evaluation of a cerebellar implementation of the TD model.