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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC Davis Electronic Theses and Dissertations (2023)

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.

    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2022)
    The cerebellum is emerging as a powerful regulator of cognitive and affective processing and memory in both humans and animals and has been implicated in affective disorders. How the cerebellum supports affective function remains poorly understood. The short-latency (just a few milliseconds) functional connections that were identified between the cerebellum and amygdala-a structure crucial for the processing of emotion and valence-more than four decades ago raise the exciting, yet untested, possibility that a cerebellum-amygdala pathway communicates information important for emotion. The major hurdle in rigorously testing this possibility is the lack of knowledge about the anatomy and functional connectivity of this pathway. Our initial anatomical tracing studies in mice excluded the existence of a direct monosynaptic connection between the cerebellum and amygdala. Using transneuronal tracing techniques, we have identified a novel disynaptic circuit between the cerebellar output nuclei and the basolateral amygdala. This circuit recruits the understudied intralaminar thalamus as a node. Using ex vivo optophysiology and super-resolution microscopy, we provide the first evidence for the functionality of the pathway, thus offering a missing mechanistic link between the cerebellum and amygdala. This discovery provides a connectivity blueprint between the cerebellum and a key structure of the limbic system. As such, it is the requisite first step toward obtaining new knowledge about cerebellar function in emotion, thus fundamentally advancing understanding of the neurobiology of emotion, which is perturbed in mental and autism spectrum disorders.
      Cover page: Novel Cerebello-Amygdala Connections Provide Missing Link Between Cerebellum and Limbic System
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