Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche UMR 7241, Institut National de la Santé et de la Recherche Médicale (INSERM) U1050, Labex Memolife, PSL-Research University, Paris, France.
Physiology and Physiopathology of the Gliovascular Unit Research Group, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche UMR 7241, Institut National de la Santé et de la Recherche Médicale (INSERM) U1050, Labex Memolife, PSL-Research University, Paris, France.
Glia. 2021 Sep;69(9):2178-2198. doi: 10.1002/glia.24017. Epub 2021 May 11.
Astrocytes play important roles in brain function via dynamic structural and functional interactions with neurons. Yet the underlying mechanisms remain poorly defined. A typical feature of astrocytes is the high expression of connexins, which mediate their extensive intercellular communication and regulate their structural properties. In particular, connexin 30 (Cx30), one of the two connexins abundantly expressed by astrocytes, was recently shown to be a critical regulator of excitatory synaptic transmission by controlling the astroglial coverage of synapses. However, the role of Cx30 in the regulation of inhibitory synaptic transmission and excitatory/inhibitory balance remains elusive. Here, we investigated the role of astroglial Cx30 on the electrophysiological and morphological properties of five classes of hippocampal CA1 stratum oriens and pyramidale neurons, defined by the unsupervised Ward's clustering. Using Cx30 knockout mice, we found that Cx30 alters specific properties of some subsets of CA1 interneurons, such as resting membrane potential and sag ratio, while other parameters, such as action potential threshold and saturation frequency, were more frequently altered among the different classes of neurons. The excitation-inhibition balance was also differentially and selectively modulated among the different neuron subtypes. Only slight morphological differences were observed on reconstructed neurons. Altogether, these data indicate that Cx30 differentially alters the electrophysiological and morphological properties of hippocampal cell populations, and modulates both their excitatory and inhibitory inputs. Astrocytes, via Cx30, are thus active modulators of both excitatory and inhibitory synapses in the hippocampus.
星形胶质细胞通过与神经元的动态结构和功能相互作用，在脑功能中发挥重要作用。然而，其潜在机制仍未得到明确界定。星形胶质细胞的一个典型特征是连接蛋白的高表达，连接蛋白介导其广泛的细胞间通讯，并调节其结构特性。特别是，星形胶质细胞中大量表达的两种连接蛋白之一，连接蛋白 30（Cx30），最近被证明是通过控制突触处的星形胶质细胞覆盖来调节兴奋性突触传递的关键调节因子。然而，Cx30 在调节抑制性突触传递和兴奋-抑制平衡中的作用仍不清楚。在这里，我们研究了星形胶质细胞 Cx30 在电生理和形态特性上对五类海马 CA1 层状和锥体神经元的作用，这五类神经元是通过无监督的 Ward 聚类定义的。使用 Cx30 基因敲除小鼠，我们发现 Cx30 改变了 CA1 中间神经元的某些亚群的特定特性，例如静息膜电位和 sag 比，而其他参数，如动作电位阈值和饱和频率，则更频繁地改变了不同类别的神经元。兴奋-抑制平衡也在不同的神经元亚型中被不同地和选择性地调节。在重建的神经元上只观察到轻微的形态差异。总之，这些数据表明 Cx30 可改变海马细胞群体的电生理和形态特性，并调节其兴奋性和抑制性输入。星形胶质细胞通过 Cx30 成为海马体中兴奋性和抑制性突触的主动调节因子。
