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

Yong-Seok Lee; Jungeun Ji; Jinhee Baek; Kyoung-Doo Hwang; Seunghwan Choi; Ted Abel; Joon-Yong An; Junko Kasuya

doi:10.21203/rs.3.rs-6469280/v1

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

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

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

Research square

05/07/2025

DOI: 10.21203/rs.3.rs-6469280/v1

PMCID: PMC12083642

PMID: 40386415

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https://doi.org/10.21203/rs.3.rs-6469280/v1View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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 + 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.

Cerebellum

deep cerebellar nuclei

single-nucleus RNA-seq

Purkinje cell layer

fear memory

spatial transcriptomics

Details

Title: Subtitle: Region- and cell type-specific changes in gene expression in the cerebellum after classical fear conditioning
Creators: Yong-Seok Lee - Seoul National University
Jungeun Ji - University of Iowa
Jinhee Baek - University of Iowa
Kyoung-Doo Hwang - University of Iowa
Seunghwan Choi - University of Iowa
Ted Abel - University of Iowa
Joon-Yong An - Korea University
Junko Kasuya - University of Iowa
Resource Type: Preprint
Publication Details: Research square
DOI: 10.21203/rs.3.rs-6469280/v1
PMID: 40386415
PMCID: PMC12083642
NLM abbreviation: Res Sq
ISSN: 2693-5015
eISSN: 2693-5015
Grant note: R01 MH087463 / NIMH NIH HHS
Language: English
Date posted: 05/07/2025
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984824299502771

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