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

**Authors:** Yong-Seok Lee, Jungeun Ji, Jinhee Baek, Kyoung-Doo Hwang, Seunghwan Choi, Ted Abel, Joon-Yong An, Junko Kasuya

PMC · DOI: 10.21203/rs.3.rs-6469280/v1 · Research Square · 2025-05-07

## TL;DR

The cerebellum undergoes region- and cell-specific gene expression changes during fear conditioning, suggesting a role in non-motor learning.

## Contribution

This study identifies region- and cell-type-specific transcriptional changes in the cerebellum following fear conditioning.

## Key findings

- Immediate early genes in the deep cerebellar nuclei are upregulated after fear learning and retrieval.
- Region-specific transcriptional changes occur in the Purkinje cell layer of the cerebellar vermis.
- Single-nucleus RNA sequencing reveals gene expression changes in Kit+ inhibitory neurons of the deep cerebellar nuclei.

## 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 that in the deep cerebellar nuclei (DCN), an output region of the cerebellum, the expression of immediate early genes increased following fear learning and retrieval, suggesting that DCN may contribute to fear memory processing. As for the cerebellar cortex, robust and region-specific transcriptional changes were observed, with distinct expression patterns emerging across the Purkinje cell layer of vermis region. To further elucidate transcriptional changes in specific DCN cell types involved in fear processing, we performed single-nucleus RNA sequencing and identified prominent gene expression 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.

## Full-text entities

- **Genes:** KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12083642/full.md

## References

93 references — full list in the complete paper: https://tomesphere.com/paper/PMC12083642/full.md

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Source: https://tomesphere.com/paper/PMC12083642