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自闭症谱系障碍样行为是由于小鼠前额叶皮层锥体神经元兴奋性突触传递减少引起的。

Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex.

机构信息

Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.

International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo, Tokyo, 113-0033, Japan.

出版信息

Nat Commun. 2020 Oct 12;11(1):5140. doi: 10.1038/s41467-020-18861-3.

DOI:10.1038/s41467-020-18861-3
PMID:33046712
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7552417/
Abstract

Autism spectrum disorder (ASD) is thought to result from deviation from normal development of neural circuits and synaptic function. Many genes with mutation in ASD patients have been identified. Here we report that two molecules associated with ASD susceptibility, contactin associated protein-like 2 (CNTNAP2) and Abelson helper integration site-1 (AHI1), are required for synaptic function and ASD-related behavior in mice. Knockdown of CNTNAP2 or AHI1 in layer 2/3 pyramidal neurons of the developing mouse prefrontal cortex (PFC) reduced excitatory synaptic transmission, impaired social interaction and induced mild vocalization abnormality. Although the causes of reduced excitatory transmission were different, pharmacological enhancement of AMPA receptor function effectively restored impaired social behavior in both CNTNAP2- and AHI1-knockdown mice. We conclude that reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons of the PFC leads to impaired social interaction and mild vocalization abnormality in mice.

摘要

自闭症谱系障碍（ASD）被认为是由于神经回路和突触功能的正常发育偏离引起的。许多在 ASD 患者中发生突变的基因已被确定。在这里，我们报告与 ASD 易感性相关的两种分子，接触蛋白相关蛋白样 2（CNTNAP2）和 Abelson 辅助整合位点 1（AHI1），对于小鼠的突触功能和 ASD 相关行为是必需的。在发育中的小鼠前额叶皮层（PFC）的第 2/3 层锥体神经元中敲低 CNTNAP2 或 AHI1 会降低兴奋性突触传递，损害社交互动并引起轻度发声异常。尽管降低兴奋性传递的原因不同，但 AMPA 受体功能的药理学增强可有效恢复 CNTNAP2 和 AHI1 敲低小鼠受损的社交行为。我们得出结论，PFC 第 2/3 层锥体神经元中的兴奋性突触传递减少导致小鼠社交互动受损和轻度发声异常。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/69d391582938/41467_2020_18861_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/50e49a923336/41467_2020_18861_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/131c16336f78/41467_2020_18861_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/fa5c9531bbe0/41467_2020_18861_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/4c85393a0da4/41467_2020_18861_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/886d561e6669/41467_2020_18861_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/69d391582938/41467_2020_18861_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/50e49a923336/41467_2020_18861_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/131c16336f78/41467_2020_18861_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/fa5c9531bbe0/41467_2020_18861_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/4c85393a0da4/41467_2020_18861_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/886d561e6669/41467_2020_18861_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c11/7552417/69d391582938/41467_2020_18861_Fig6_HTML.jpg

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本文引用的文献

[1]
Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

Mol Psychiatry. 2021-8

[2]
Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome.

Nat Commun. 2019-8-6

[3]
The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex.

Neuron. 2019-6-20

[4]
Role of VTA dopamine neurons and neuroligin 3 in sociability traits related to nonfamiliar conspecific interaction.

Nat Commun. 2018-8-9

[5]
Pharmacological modulation of AMPA receptor rescues social impairments in animal models of autism.

Neuropsychopharmacology. 2018-5-22

[6]
SHANK proteins: roles at the synapse and in autism spectrum disorder.

Nat Rev Neurosci. 2017-2-9

[7]
Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex.

Proc Natl Acad Sci U S A. 2016-11-8

[8]
Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice.

Nat Commun. 2016-9-1

[9]
Maternal Deprivation Influences Pup Ultrasonic Vocalizations of C57BL/6J Mice.

PLoS One. 2016-8-23

[10]
Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons.

Science. 2016-5-6

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