Park Jiho, Sipe Grayson O, Tang Xin, Ojha Prachi, Fernandes Giselle, Leow Yi Ning, Zhang Caroline, Osako Yuma, Natesan Arundhati, Drummond Gabrielle T, Jaenisch Rudolf, Sur Mriganka
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 01239, USA.
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
bioRxiv. 2024 Nov 7:2024.11.06.622321. doi: 10.1101/2024.11.06.622321.
Astrocytes, which are increasingly recognized as pivotal constituents of brain circuits governing a wide range of functions, express GABA transporter 3 (Gat3), an astrocyte-specific GABA transporter responsible for maintenance of extra-synaptic GABA levels. Here, we examined the functional role of Gat3 in astrocyte-mediated modulation of neuronal activity and information encoding. First, we developed a multiplexed CRISPR construct applicable for effective genetic ablation of Gat3 in the visual cortex of adult mice. Using two-photon calcium imaging of visual cortex neurons in Gat3 knockout mice, we observed changes in spontaneous and visually driven single neuronal response properties such as response magnitudes and trial-to-trial variability. Gat3 knockout exerted a pronounced influence on population-level neuronal activity, altering the response dynamics of neuronal populations and impairing their ability to accurately represent stimulus information. These findings demonstrate that Gat3 in astrocytes profoundly shapes the sensory information encoding capacity of neurons and networks within the visual cortex.
星形胶质细胞越来越被认为是控制广泛功能的脑回路的关键组成部分，它表达γ-氨基丁酸转运体3（Gat3），这是一种星形胶质细胞特异性γ-氨基丁酸转运体，负责维持突触外γ-氨基丁酸水平。在这里，我们研究了Gat3在星形胶质细胞介导的神经元活动调节和信息编码中的功能作用。首先，我们开发了一种多重CRISPR构建体，适用于在成年小鼠视觉皮层中有效基因敲除Gat3。通过对Gat3基因敲除小鼠视觉皮层神经元进行双光子钙成像，我们观察到自发和视觉驱动的单个神经元反应特性的变化，如反应幅度和逐次试验变异性。Gat3基因敲除对群体水平的神经元活动产生了显著影响，改变了神经元群体的反应动力学，并损害了它们准确表征刺激信息的能力。这些发现表明，星形胶质细胞中的Gat3深刻地塑造了视觉皮层内神经元和神经网络的感觉信息编码能力。
