Region- and cell type-specific changes in gene expression in the cerebellum after classical fear conditioning

Abstract The cerebellum has recently been recognized for its role in non-motor functions, including classical fear conditioning. However, the molecular mechanisms underlying non-motor learning and memory remain largely unknown. Here, we investigate the transcriptional changes in the cerebellum associated with auditory fear conditioning. Spatial transcriptomic analysis revealed elevated expression of immediate early genes in the deep cerebellar nuclei (DCN), an output region of the cerebellum, following fear conditioning (CD) and tone retrieval (TN), suggesting that the DCN may contribute to fear memory processing. To further elucidate transcriptional changes in specific DCN cell types involved in fear processing, we performed single-nucleus RNA sequencing and identified prominent transcriptional changes in Kit+ inhibitory neurons. Collectively, our findings highlight region- and cell-type-specific molecular adaptations in the cerebellum, providing insights into its contribution to non-motor learning.