Cerebellar Interactions with the Amygdala and Prefrontal Cortex during Learning

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Learning is how organisms adapt to changes in their environment and involves the coordination of neural systems mediating cognition, emotion, and motor control. The major goal of the proposed research program is to elucidate the neural circuit mechanisms underlying interactions between cognitive, emotional, and motor systems during associative learning. Interactions between these neural systems are particularly important because the context and emotional significance of stimuli provide essential information for acquisition and performance of motor responses. The breakdown of interactions between cognitive, emotional, and motor systems in various neurological disorders can therefore have devastating consequences for learned behaviors. The prefrontal cortex, amygdala, and cerebellum play significant roles in cognition, emotional responses, and motor learning, respectively. The proposed research program constitutes a comprehensive analysis of cerebellar interactions with the amygdala and prefrontal cortex during associative motor learning. Our general conceptual framework is that the cerebellum receives inputs from the amygdala and prefrontal cortex via the pons regarding which stimuli are important and when they occur, and the cerebellum then sends error-driven feedback to these forebrain systems to facilitate learning about important events. This conceptual framework takes into account the bidirectional relationship between the cerebellum and the relevant forebrain systems as well as interactions between forebrain systems. Multi-site electrophysiology, pathway-specific optogenetics, and precise behavioral analyses will be combined to investigate circuit-level interactions between the cerebellum, amygdala, and prefrontal cortex during associative learning and extinction (inhibitory learning) training. The proposed studies would significantly advance understanding of the neural circuit mechanisms underlying cerebellar interactions with the forebrain. This would be a substantial contribution to the field because it has been known that the cerebellum must interact with the forebrain in many contexts that are crucial for everyday life such as learning, memory, planning, control of emotions, and communication, but very little is known mechanistically about how the cerebellum interacts with the amygdala and prefrontal cortex.