Instituto Cajal (CSIC), Madrid, Spain.
NYU Neuroscience Institute, New York University Langone Medical Center, New York, NY, USA.
Nat Neurosci. 2021 Jan;24(1):82-92. doi: 10.1038/s41593-020-00752-x. Epub 2020 Dec 7.
GABA interneurons play a critical role in higher brain functions. Astrocytic glial cells interact with synapses throughout the whole brain and are recognized as regulatory elements of excitatory synaptic transmission. However, it is largely unknown how GABAergic interneurons and astrocytes interact and contribute to stable performance of complex behaviors. Here, we found that genetic ablation of GABA receptors in medial prefrontal cortex astrocytes altered low-gamma oscillations and firing properties of cortical neurons, which affected goal-directed behaviors. Remarkably, working memory deficits were restored by optogenetic stimulation of astrocytes with melanopsin. Furthermore, melanopsin-activated astrocytes in wild-type mice enhanced the firing rate of cortical neurons and gamma oscillations, as well as improved cognition. Therefore, our work identifies astrocytes as a hub for controlling inhibition in cortical circuits, providing a novel pathway for the behaviorally relevant midrange time-scale regulation of cortical information processing and consistent goal-directed behaviors.
GABA 能中间神经元在大脑高级功能中发挥着关键作用。星形胶质细胞与整个大脑中的突触相互作用，被认为是兴奋性突触传递的调节因子。然而，GABA 能中间神经元和星形胶质细胞如何相互作用以及如何有助于复杂行为的稳定表现，在很大程度上尚不清楚。在这里，我们发现，内侧前额叶皮层星形胶质细胞中 GABA 受体的基因缺失改变了皮质神经元的低γ波振荡和放电特性，从而影响了目标导向行为。值得注意的是，通过光遗传学刺激黑视蛋白激活星形胶质细胞可恢复工作记忆缺陷。此外，野生型小鼠中黑视蛋白激活的星形胶质细胞增强了皮质神经元的放电率和γ波振荡，并改善了认知。因此，我们的工作确定星形胶质细胞作为控制皮质回路中抑制作用的中枢，为皮质信息处理和一致的目标导向行为的行为相关中程时间尺度调节提供了新的途径。
