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Examination of Novel Circuits Linking the Cerebellum and Nucleus Accumbens

Abstract

Although the cerebellum is now recognized as part of a long-range brain network that serves limbic functions and motivated behavior, knowledge of cerebello-limbic connectivity is limited, and nearly nothing is known about how the cerebellum connects functionally to the nucleus accumbens (NAc), a region well-known for its role in social, reward, and motivated behaviors. In my first chapter, I report the first electrophysiological evidence that stimulation of cerebellar nuclei in mice of both sexes modulates spiking activity in both NAc core and medial shell. NAc neurons respond with fast excitation and slower, less synchronized inhibition. Fast responses would be well poised to support rapid communication of information critical to the control of motivated behavior, whereas slower responses may be suggestive of a regulatory function, such as gain control. In my second chapter I describe anatomical connections via tracing experiments to chart cerebellar nuclei-NAc pathways identified disynaptic pathways that recruit the ventral tegmental area (VTA) and intralaminar thalamus (Centromedial and Parafascicular nuclei) as intermediary, monosynaptically-connected nodes. Optogenetic activation of cerebellar axons in each of these nodes was sufficient to evoke responses, primarily excitatory, in both NAc core and medial shell. These pathways and the functional connectivity they support could underlie the role of the cerebellum in motivated behavior and further elucidate our growing understanding of the non-motor cerebellum.

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