Functional connectivity in a novel cerebellar-amygdala circuit that regulates fear extinction

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ABSTRACT The cerebellum (CB) has long been considered a purely motor structure; however, studies over the last few decades have revealed vital, non-motor functions as well, including a key role in limbic processing. The cerebellum is involved in both the experience of emotion and in controlling the appropriate autonomic, cognitive, and behavioral responses, and plays an important part in all phases of emotional memory, including acquisition, consolidation, storage and retrieval, and extinction. Dysfunctions of the cerebellum have been associated with various neurological and neuropsychiatric disorders such as cognitive affective syndrome, schizophrenia, anxiety, and depression. To accomplish so much in both the motor and cognitive domains, the cerebellum is thought to integrate diverse inputs and send predictions about optimal behavioral outputs to the rest of the brain. However, the pathways and mechanisms involved in this type of processing remain poorly understood. My lab has recently discovered novel disynaptic pathways connecting the cerebellum and the amygdala via the intralaminar thalamus (Th) (centromedial and parafascicular nuclei) and ventral tegmental area (VTA) which may play a fundamental role in these expanded cognitive and emotional functions. The experiments outlined in this proposal will focus on examining if the novel cerebello-thalamo-amygdala pathway is involved in fear extinction learning, where signals about unexpected outcomes are thought to guide changes in behavior. In these experiments, I will measure activity in the pathway using calcium imaging with fiber photometry and manipulate signaling with optogenetics. In tandem, in slice electrophysiology experiments, I will examine the cellular and synaptic properties of CB-Th connectivity. Together, this proposal will provide novel insights into what the cerebellum might be doing in the context of emotional learning, the necessity of the specific pathway in non-motor behavior, and the signaling properties within each microcircuit. These explorations will add to our understanding of cerebellar limbic functions and help guide future studies of how these circuits may be impaired in neuropsychiatric disorders to propel the search for more effective treatments.