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Open Access Publications from the University of California

Cerebellar Regulation of Fear Extinction Through the Limbic Thalamus

Abstract

The cerebellum is an established regulator of motor control and has recently garnered novel focus for its modulation of affective processes. We previously characterized cerebellar projections to the parafascicular nucleus (PF), which modulates orienting responses and behavioral alertness. We identified an anatomical circuit between the deep cerebellar nuclei (DCN) and the basolateral nucleus of the amygdala (BLA) through the PF. Here we provide functional characterization of this circuit and examine whether and how the circuit might regulate affective processing. We show that optogenetic stimulation of DCN-PF projections reduces c-Fos expression in PF and modulates BLA neural activity. We optogenetically inhibited the DCN-PF projections during distinct phases of auditory fear conditioning. Optoinhibition during training has no consequence, but during extinction it results in faster extinction. This effect on extinction appears to be specific to the DCN-PF projection: optoinhibition of cerebellar projections to the centromedial thalamic nucleus (CM), an intermediary node between the cerebellum and amygdala, does not appear to modulate fear acquisition or extinction. Ongoing work is capturing potential neural signatures of fear regulation. Overall, our findings reveal a novel functional divergence between limbic projections of the cerebellum and establish future targets for exploring affective processes of relevance to neuropsychiatric disorders.