Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning

Multiple brain regions are engaged in classical fear conditioning. Despite evidence for cerebellar involvement in fear conditioning, the mechanisms by which cerebellar outputs modulate fear learning and memory remain unclear. We identify a population of deep cerebellar nucleus (DCN) neurons with monosynaptic glutamatergic projections to the lateral parabrachial nucleus (lPBN) (DCN-'lPBN neurons) in mice. While optogenetic sup-pression of DCN-'lPBN neurons impairs auditory fear memory, activation of DCN-'lPBN neurons elicits freezing behavior only after auditory fear conditioning. Moreover, auditory fear conditioning potentiates DCN-lPBN synapses, and subsequently, auditory cue activates lPBN neurons after fear conditioning. Furthermore, DCN-'lPBN neuron activation can replace the auditory cue but not footshock in fear conditioning. These findings demonstrate that cerebellar nuclei modulate auditory fear conditioning via transmitting conditioned stimuli signals to the lPBN. Collectively, our findings suggest that the DCN-lPBN circuit is a part of neuronal substrates within interconnected brain regions underscoring auditory fear memory.

Automated summary

This study identifies a population of neurons in the deep cerebellar nucleus (DCN) with monosynaptic glutamatergic projections to the lateral parabrachial nucleus (lPBN). Suppression of these DCN-lPBN neurons impairs auditory fear memory, while their activation leads to freezing behavior after auditory fear conditioning. Conditioning strengthens the synapses between DCN and lPBN, and following fear conditioning, the auditory cue activates lPBN neurons. Furthermore, activation of DCN-lPBN neuron can replace the auditory cue but not footshock in fear conditioning. These findings suggest that the DCN-lPBN circuit plays a role in modulating auditory fear conditioning.