GABAergic inhibitory neurons are the principal source of inhibition in the brain. Traditionally, their role in maintaining the balance of excitation-inhibition has been emphasized. Beyond homeostatic functions, recent circuit mapping and functional manipulation studies have revealed a wide range of specific roles that GABAergic circuits play in dynamically tilting excitation-inhibition coupling across spatio-temporal scales. These span from gating of compartment- and input-specific signaling, gain modulation, shaping input–output functions and synaptic plasticity, to generating signal-to-noise contrast, defining temporal windows for integration and rate codes, as well as organizing neural assemblies, and coordinating inter-regional synchrony. GABAergic circuits are thus instrumental in controlling single-neuron computations and behaviorally-linked network activity. The activity dependent modulation of sensory and mnemonic information processing by GABAergic circuits is pivotal for the formation and maintenance of episodic memories in the hippocampus. Here, we present an overview of the local and long-range GABAergic circuits that modulate the dynamics of excitation-inhibition and disinhibition in the main output area of the hippocampus CA1, which is crucial for episodic memory. Specifically, we link recent findings pertaining to GABAergic neuron molecular markers, electrophysiological properties, and synaptic wiring with their function at the circuit level. Lastly, given that area CA1 is particularly impaired during early stages of Alzheimer’s disease, we emphasize how these GABAergic circuits may contribute to and be involved in the pathophysiology.

中文翻译：

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海马 CA1 区的局部和远程 GABA 能回路及其与阿尔茨海默病的联系

GABA 能抑制神经元是大脑抑制的主要来源。传统上，人们强调它们在维持兴奋-抑制平衡方面的作用。除了稳态功能之外，最近的电路图谱和功能操纵研究揭示了 GABA 能电路在跨时空尺度的动态倾斜兴奋-抑制耦合中发挥的广泛特定作用。这些范围从隔室和输入特定信号的门控、增益调制、塑造输入输出功能和突触可塑性，到生成信噪比、定义积分和速率代码的时间窗口，以及组织神经组件，并协调区域间同步。因此，GABA 能电路有助于控制单神经元计算和行为相关的网络活动。GABA 电路对感觉和记忆信息处理的活动依赖性调节对于海马情景记忆的形成和维持至关重要。在这里，我们概述了调节海马 CA1 主要输出区域的兴奋抑制和去抑制动态的局部和远程 GABA 能回路，这对于情景记忆至关重要。具体来说，我们将有关 GABA 能神经元分子标记、电生理特性和突触布线的最新发现与其在电路水平上的功能联系起来。最后，鉴于 CA1 区在阿尔茨海默病的早期阶段尤其受损，我们强调这些 GABA 能回路如何促进并参与病理生理学。