Emotions play a tremendous role in our lives - creating priorities, shaping values, and guiding our most important choices. Recent studies demonstrate that learning and memory in humans is much more profoundly affected by emotion than was previously assumed. The long-term goal is to understand how the amygdala and related brain regions are involved in emotional learning and memory. This requires elucidating the necessary and modulatory structures involved in emotional learning. The model preparation for studying aversive Pavlovian learning entails conditioned enhancement of the rat eyeblink reflex. The short-latency (R1) electromyographic component of the blink reflex offers several advantages as an index of emotional learning. The proposed methods combine neurophysiology, neuroanatomy, behavior and computational modeling. A general working hypothesis has been developed, an associated computational model, and a behavioral paradigm for evaluating the role of the amygdala and perirhinal cortex in forming associations between a conditioned stimulus (CS) and an unconditioned stimulus (US) and for encoding the CS-US interval during aversive conditioning. The computational model is the first to show how certain temporal aspects of associative learning emerge from the cellular neurobiology and circuitry. The approach allows vertical integration, traversing several levels of organization - from synapses to circuits to behavior. The model serves as the current hypothesis and also as the theoretical glue that binds information within and among levels and helps us understand and test various proposed hypotheses. In pursuit of the goal of vertical integration, the system selected for study enables one to go back and forth between in vitro and in vivo analysis, and the technology to do so is available (although the present proposal is concerned with in vivo studies). One goal is to demystify some of the psychological components of certain disorders by understanding the circuitry involved in emotional learning and to develop testable hypothesis for explaining biological changes that occur during stressful situations. The information and technology should be relevant to insights into, and treatment of, both psychiatric and neurological disorders (anxiety, stress, panic, cognitive impairment, blepharospasm, and epilepsy). By design, the approach is extendible into aging-related problems.
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