Synaptic Regulation of Innate Freezing by the Fastigial Nucleus of the Cerebellum

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Continuous, modulated cerebellar output is required for ongoing movements, and the suppression of cerebellar output, either via lesions or inactivation, impedes even well practiced movements. However, whether changes in cerebellar output can directly drive the transition into a unique motor state has not been explored. Freezing, as occurs during both innate and conditioned defense behaviors, is a motor state involving the suppression of voluntary movement while maintaining and elevated arousal state and muscle tone. Such freezing responses require activation of the ventro-lateral periaqueductal gray, which, receives input from the fastigial cerebellar nucleus. In fact, previous work indicates that lesion of the cerebellar vermis impairs innate freezing behaviors, suggesting that cerebellar output might modulate freezing behaviors mediated by the periaqueductal gray. Despite these findings, the role of the fastigial nucleus in modulating the firing rate of neurons in the ventro- lateral periaqueductal gray has not been explicitly tested. Here, I will test the hypothesis that (1) activity in the fastigial cerebellar nucleus modulates firing in the PAG and regulates innate freezing and (2) that sex differences in the synaptic and intrinsic properties within the fastigial cerebellar nucleus contribute to differences in innate freezing. To do this, I propose to use a combination of in vitro and in vivo electrophysiology in both the fastigial cerebellar nucleus and the ventro-lateral periaqueductal gray to explicitly examine how the spontaneous and synaptically evoked activity in the fastigial cerebellar nucleus modulates spiking patterns in the ventro-lateral periaqueductal gray. Then, using in vivo recordings and directly manipulating fastigial neuron activity using optogenetics, I will examine whether activation or suppression of cerebellar activity is sufficient to drive freezing behaviors. Together, these experiments will directly test whether synaptically evoked changes in cerebellar output can drive freezing, and provide experimental insight into how cerebellar output is integrated in downstream nuclei to drive behavior.