Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities.
Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities.
复制标题
DOI：
10.1016/j.neuron.2020.03.025
复制
发表时间：
2020-06-17
期刊：
影响因子：
16.2
通讯作者：
Deneen B
中科院分区：
文献类型：
--
作者：
Huang AY;Woo J;Sardar D;Lozzi B;Bosquez Huerta NA;Lin CJ;Felice D;Jain A;Paulucci-Holthauzen A;Deneen B
星形胶质细胞通过支持突触连接和相关电路在大脑功能中发挥重要作用。这些作用如何受转录因子调节尚不清楚。此外，越来越多的证据表明星形胶质细胞表现出区域异质性，而控制这种多样性的机制仍处于萌芽状态。在这里，我们表明，成人大脑星形胶质细胞中转录因子 NFIA 的条件性缺失会导致由选择性 DNA 结合介导的形态和生理学的区域特异性改变。 NFIA 丧失后星形胶质细胞功能的破坏在海马体中最为明显，表现为与神经元的相互作用受损，以及学习和记忆行为的减弱。海马星形胶质细胞中的这些变化并不影响基底神经元特性，但特别抑制了突触可塑性，突触可塑性由星形胶质细胞中的 NFIA 通过钙依赖性机制进行调节。总之，我们的研究揭示了星形胶质细胞的区域特异性转录依赖性，并确定星形胶质细胞 NFIA 是海马回路的关键转录调节因子。星形胶质细胞通过支持突触连接和相关电路在大脑功能中发挥重要作用。我们发现转录因子 NFIA 是通过区域特异性 DNA 结合机制维持海马星形胶质细胞功能所必需的。星形胶质细胞-神经元通讯的改变会扰乱海马回路功能，导致学习和记忆行为受损。
Astrocytes play essential roles in brain function by supporting synaptic connectivity and associated circuits. How these roles are regulated by transcription factors is unknown. Moreover, there is emerging evidence that astrocytes exhibit regional heterogeneity and the mechanisms controlling this diversity remain nascent. Here we show that conditional deletion of the transcription factor NFIA in astrocytes in the adult brain results in region-specific alterations in morphology and physiology that are mediated by selective DNA binding. Disruptions in astrocyte function following loss of NFIA are most pronounced in the hippocampus, manifested by impaired interactions with neurons, coupled with diminution of learning and memory behaviors. These changes in hippocampal astrocytes did not affect basal neuronal properties, but specifically inhibited synaptic plasticity, which is regulated by NFIA in astrocytes through calcium-dependent mechanisms. Together, our studies reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits. Astrocytes play essential roles in brain function by supporting synaptic connectivity and associated circuits. We found the transcription factor NFIA is required to maintain astrocyte function in the hippocampus, through region-specific DNA binding mechanisms. Alterations in astrocyte-neuron communication disrupt hippocampal circuit function, resulting in impaired learning and memory behaviors.
登录
查看更多内容
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
3
作者：
Fitzgerald BJ;Richardson K;Wesson DW
通讯作者：
Wesson DW
影响因子：
16.2
作者：
Abraham NM;Egger V;Shimshek DR;Renden R;Fukunaga I;Sprengel R;Seeburg PH;Klugmann M;Margrie TW;Schaefer AT;Kuner T
通讯作者：
Kuner T
影响因子：
3.4
作者：
Gordon, GW;Berry, G;Herman, B
通讯作者：
Herman, B
来自小鼠大脑多个区域的老化星形胶质细胞转录组。
影响因子：
8.8
作者：
Boisvert MM;Erikson GA;Shokhirev MN;Allen NJ
通讯作者：
Allen NJ