UC Davis

The cerebellum (CB) has long been considered a purely motor structure. However, studies over the last few decades have revealed vital contributions of the cerebellum to a wide array of non-motor functions including a key role in limbic processing. The CB 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. Cerebellar dysfunction has 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 CB 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. The goal of my dissertation was to investigate how the CB may coordinate limbic processing through newly discovered long-range circuits. Chapter 2 details anatomical and electrophysiological evidence for new pathways connecting the CB to the amygdala through the limbic thalamus, in particular the centromedial (CM) and parafascicular (PF) nuclei. This includes rigorous anatomical tracing as well as mechanistic analysis using ex vivo slice electrophysiology combined with fine-tuned pharmacological and optogenetic manipulations to establish evidence for synaptic connectivity. In Chapter 3, we investigated connections from the cerebellum to the nucleus accumbens (NAc) through nodes in the CM and PF thalamus and the ventral tegmental area (VTA) using anatomical tracing, in vivo electrophysiology, and circuit specific optogenetic manipulations. Finally, Chapter 4 summarizes an investigation into the functional role of the CB-PF circuit in fear memory, extinction learning, and anxiety using targeted optogenetic manipulations of projections during behavioral tasks as well as in vivo electrophysiological recordings to test connectivity with the BLA. Overall, this dissertation details work which has provided novel insights into the cerebellum’s role in the context of emotional learning, the necessity of specific pathways in non-motor behavior, and the signaling properties within the relevant circuits.