Optogenetic stimulation of Purkinje cells in the cerebellar vermis disrupts innate freezing behaviors and is highly aversive

Abstract

The generation of adaptive defensive behaviors in response to predator threats requires the integration of sensory inputs by neural circuits to shape context-appropriate motor outputs. While the cerebellum is increasingly recognized as a contributor to non-motor behaviors, its role in regulating innate fear behaviors is only beginning to be recognized. For example, it is unclear whether and how cerebellar activity influences both the expression and experience-dependent habituation of defensive responses to ethologically relevant stimuli. Here, we examine how manipulation of cerebellar output alters innate freezing behavior and its adaptation across repeated predator-like visual stimuli. Using optogenetic stimulation of vermal Purkinje cells, we demonstrate that ongoing fastigial nucleus (FN) activity is required for the generation of appropriate freezing behaviors and further that perturbations of FN activity alter adaptive habituation across repeated trials at both short (5 minute) and long (24 hour) intervals. Our results suggest that cerebellar stimulation results in an elevated fear state, as stimulation was both anxiogenic in an open field arena and resulted in robust real-time place aversion that resisted reversal learning. Together, these findings identify the cerebellum as a key regulator of both the expression and experience-dependent adaptation of innate fear responses.