Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice.
Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice.
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在ASD相关的CHD8单倍弹性小鼠的皮质电路中，细胞型特异性突触失衡和稳态可塑性破坏。
DOI：
10.1038/s41380-021-01070-9
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发表时间：
2021-07
影响因子：
11
通讯作者：
Andreae LC
中科院分区：
文献类型：
--
作者：
Ellingford RA;Panasiuk MJ;de Meritens ER;Shaunak R;Naybour L;Browne L;Basson MA;Andreae LC
染色体结构域解旋酶DNA结合蛋白8（chromodomain helicase DNA binding protein 8，CHD8）的杂合突变与自闭症谱系障碍（autism spectrum disorder，ASD）密切相关，并导致脑发育过程中神经发育和突触基因的表达失调。为了揭示这些变化如何影响ASD相关的皮层回路，我们研究了单倍不足的Chd8小鼠模型的前额叶皮层中的突触传递。我们报告了深层投射神经元的兴奋性和抑制性突触传递的深刻变化，导致兴奋性：抑制性平衡降低，这被发现在神经发育过程中动态变化，并导致单个神经元亚型内Chd8表达降低的不同影响。这些变化与通过自发神经传递的稳态可塑性机制的调节中断有关。因此，这些发现直接暗示CHD8突变破坏了皮质中ASD相关回路。
Heterozygous mutation of chromodomain helicase DNA binding protein 8 (CHD8) is strongly associated with autism spectrum disorder (ASD) and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. To reveal how these changes affect ASD-associated cortical circuits, we studied synaptic transmission in the prefrontal cortex of a haploinsufficient Chd8 mouse model. We report profound alterations to both excitatory and inhibitory synaptic transmission onto deep layer projection neurons, resulting in a reduced excitatory:inhibitory balance, which were found to vary dynamically across neurodevelopment and result from distinct effects of reduced Chd8 expression within individual neuronal subtypes. These changes were associated with disrupted regulation of homeostatic plasticity mechanisms operating via spontaneous neurotransmission. These findings therefore directly implicate CHD8 mutation in the disruption of ASD-relevant circuits in the cortex.
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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
影响因子：
4.3
作者：
Barnard RA;Pomaville MB;O'Roak BJ
通讯作者：
O'Roak BJ
影响因子：
4.6
作者：
Latcheva, Nina K.;Delaney, Taylor L.;Liebl, Faith L. W.
通讯作者：
Liebl, Faith L. W.
影响因子：
5.3
作者：
Angel Garcia-Bereguiain, Miguel;Gonzalez-Islas, Carlos;Wenner, Peter
通讯作者：
Wenner, Peter
影响因子：
5.3
作者：
Baker, Arielle;Kalmbach, Brian;Dembrow, Nikolai
通讯作者：
Dembrow, Nikolai