Coordinated cerebellar–midbrain activity for predictive signaling during fear learning in mice
Year: 2026
Type: preprint
Abstract: SUMMARY Learning from experience to assess threat is crucial for survival and mental health. This function is known to involve several midbrain areas, notably the ventrolateral periaqueductal grey (vlPAG) and dorsal raphe nuclei (DRN). Recently it has been shown that fear learning involves projections from the cerebellar fastigial nucleus (FN) to the vlPAG. Here, we show using simultaneous single-unit recordings during fear conditioning that a subset of vlPAG/DRN and FN neurons acquire responses to conditioned cues following learning. Strikingly, these populations exhibit firing covariance and directional functional interactions consistent with their collaboration to the response to cues predicting threat. We also demonstrated the reciprocal monosynaptic connectivity between vlPAG/DRN and FN supporting the interactions between these structures. Together, our findings demonstrate shared dynamical activity within a network integrating midbrain and cerebellar computations during fear learning. IN BRIEF The projections of the cerebellar fastigial nucleus (FN) to the midbrain are involved in associative fear learning. Here, we show that during fear learning FN and periaqueductal grey/dorsal raphe (vlPAG/DRN) neurons acquire simultaneously responses to stimuli predicting aversive stimulus. Moreover, neurons encoding such predictive signals in the FN exhibit coordinated activity with the vlPAG/DRN, with directional functional interactions, suggesting that cerebellar – midbrain interactions contribute to the representation of aversive predictions during fear learning. We further characterize monosynaptic projections from the vlPAG/DRN to the contralateral FN, providing an anatomical substrate for reciprocal communications between the cerebellum and midbrain and extending previous descriptions of this pathway. HIGHLIGHTS - Cerebellar fastigial (FN) neurons acquire stimulus specific predictive signals during fear learning. - FN neurons encoding predictive signals exhibit coordinated activity and directional functional interactions with vlPAG/DRN neurons. - vlPAG/DRN neurons projecting to the FN elicit short-latency responses in FN neurons. - Reciprocal projections link the FN and vlPAG/DRN providing a potential substrate for cerebellar-midbrain interactions during fear learning.
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223187102