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经典恐惧条件反射后小脑基因表达的区域和细胞类型特异性变化。

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

作者信息

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

机构信息

Seoul National University College of Medicine.

University of Iowa.

出版信息

Res Sq. 2025 May 7:rs.3.rs-6469280. doi: 10.21203/rs.3.rs-6469280/v1.


DOI:10.21203/rs.3.rs-6469280/v1
PMID:40386415
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12083642/
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.

摘要

小脑最近因其在非运动功能中的作用而受到认可,包括经典恐惧条件反射。然而,非运动学习和记忆背后的分子机制在很大程度上仍然未知。在这里,我们研究了与听觉恐惧条件反射相关的小脑转录变化。空间转录组分析显示,在小脑深部核团(DCN),即小脑的一个输出区域,立即早期基因的表达在恐惧学习和回忆后增加,这表明DCN可能有助于恐惧记忆处理。至于小脑皮质,观察到了强烈且区域特异性的转录变化,在蚓部区域的浦肯野细胞层出现了不同的表达模式。为了进一步阐明参与恐惧处理的特定DCN细胞类型中的转录变化,我们进行了单核RNA测序,并在 + 抑制性神经元中鉴定出显著的基因表达变化。总的来说,我们的研究结果突出了小脑中区域和细胞类型特异性的分子适应性,为其对非运动学习的贡献提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/5ad9fd10c41f/nihpp-rs6469280v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/72a1243f2083/nihpp-rs6469280v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/940bc20013de/nihpp-rs6469280v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/af91822dae90/nihpp-rs6469280v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/0743dff48162/nihpp-rs6469280v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/fc41fde62ab7/nihpp-rs6469280v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/5ad9fd10c41f/nihpp-rs6469280v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/72a1243f2083/nihpp-rs6469280v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/940bc20013de/nihpp-rs6469280v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/af91822dae90/nihpp-rs6469280v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/0743dff48162/nihpp-rs6469280v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/fc41fde62ab7/nihpp-rs6469280v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9315/12083642/5ad9fd10c41f/nihpp-rs6469280v1-f0006.jpg

相似文献

[1]
Region- and cell type-specific changes in gene expression in the cerebellum after classical fear conditioning.

Res Sq. 2025-5-7

[2]
Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning.

Cell Rep. 2023-4-25

[3]
Roles of Cbln1 in Non-Motor Functions of Mice.

J Neurosci. 2016-11-16

[4]
Model-Driven Analysis of Eyeblink Classical Conditioning Reveals the Underlying Structure of Cerebellar Plasticity and Neuronal Activity.

IEEE Trans Neural Netw Learn Syst. 2017-11

[5]
Perineuronal Nets in the Deep Cerebellar Nuclei Regulate GABAergic Transmission and Delay Eyeblink Conditioning.

J Neurosci. 2018-6-1

[6]
Population coding in the cerebellum: a machine learning perspective.

J Neurophysiol. 2020-12-1

[7]
Inhibition of the amygdala central nucleus by stimulation of cerebellar output in rats: a putative mechanism for extinction of the conditioned fear response.

Eur J Neurosci. 2014-11

[8]
Catecholaminergic Innervation of the Lateral Nucleus of the Cerebellum Modulates Cognitive Behaviors.

J Neurosci. 2021-4-14

[9]
Cerebellum and Emotion Memory.

Adv Exp Med Biol. 2022

[10]
Cerebellar modulation of memory encoding in the periaqueductal grey and fear behaviour.

Elife. 2022-3-15

本文引用的文献

[1]
Transthyretin Amyloidosis: Role of oxidative stress and the beneficial implications of antioxidants and nutraceutical supplementation.

Neurochem Int. 2024-10

[2]
Specialized connectivity of molecular layer interneuron subtypes leads to disinhibition and synchronous inhibition of cerebellar Purkinje cells.

Neuron. 2024-7-17

[3]
A role for the cerebellum in motor-triggered alleviation of anxiety.

Neuron. 2024-4-3

[4]
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain.

Nature. 2023-12

[5]
Climbing fiber multi-innervation of mouse Purkinje dendrites with arborization common to human.

Science. 2023-7-28

[6]
Purkinje cell microzones mediate distinct kinematics of a single movement.

Nat Commun. 2023-7-19

[7]
Selenoproteins synergistically protect porcine skeletal muscle from oxidative damage via relieving mitochondrial dysfunction and endoplasmic reticulum stress.

J Anim Sci Biotechnol. 2023-6-4

[8]
Glutamatergic cerebellar neurons differentially contribute to the acquisition of motor and social behaviors.

Nat Commun. 2023-5-15

[9]
Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning.

Cell Rep. 2023-4-25

[10]
The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice.

Nat Commun. 2023-3-17

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