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

Kyoung‐Doo Hwang, Jinhee Baek, Hyun-Hee Ryu, Jaegeon Lee, Hyun Geun Shim, Sun Yong Kim, Sang Jeong Kim, Yong‐Seok Lee, Sang Jeong Kim, Yong‐Seok Lee

2023Cell Reports22 citationsDOIOpen Access PDF

Abstract

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 suppression 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.

Topics & Concepts

NeuroscienceFear conditioningOptogeneticsLateral parabrachial nucleusPsychologyConditioningGlutamatergicParabrachial NucleusFear processing in the brainClassical conditioningNucleusChemistryAmygdalaGlutamate receptorMathematicsBiochemistryReceptorStatisticsNeuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeuroendocrine regulation and behavior