In the hippocampus, GABA inhibition tunes network oscillations and shapes synchronous activity during spatial learning and memory coding. Once released from the presynapse, GABA primarily binds to ionotropic GABA_A receptors (GABA_ARs), which are heteropentamers combinatorially assembled from nineteen known subunits to induce Cl^- currents postsynaptically. Dissecting GABA_AR subtype specificities in neurobiology is daunting because of differences in their developmental dynamics, regional distribution and subcellular compartmentalization. Here, we review recent data to show that the combination of single-cell mRNA-seq and neuroanatomy can reveal unprecedented cell-type and network-specificity of GABA_AR subunits and limit the permutation in subunit configurations, thus rationalizing GABA_AR physiology and pharmacology. By comparing RNA-seq data on principal cells and interneurons we discuss a tight match between GABA_AR subunit allocation, diversity in the origins of GABA inputs and operational rules at synaptic and extrasynaptic sites. We propose that coincident analysis of all GABA_AR subunits, particularly in relation to specific behaviors, could overcome existing pitfalls of the genetic and pharmacological manipulation of single subunits. By using α1 and α5 GABA_AR subunits, we single out hippocampal spatial learning as a process in which, despite the many studies available to date, neither consensus nor causality exists with regards to GABA_AR subtype requirements, curtailing a unifying concept on postsynaptic coding of GABA signals. Finally, we address the modulation of GABA_AR subunits by dopamine and endocannabinoids through receptor heteromerization, cross-modulation of signal transduction and allostery. In sum, data in this review infer that multiparametric computation gains momentum to improve knowledge on GABA_ARs function in cognition and neuropsychiatric illnesses.

在海马体中，GABA 抑制在空间学习和记忆编码过程中调节网络振荡并塑造同步活动。一旦从突触前释放，GABA 主要与离子型 GABA _A受体 (GABA _A Rs) 结合，这些受体是由 19 个已知亚基组合组装而成的异五聚体，可在突触后诱导 Cl ^-电流。在神经生物学中剖析 GABA _A R 亚型特异性是令人生畏的，因为它们的发育动力学、区域分布和亚细胞区室化存在差异。在这里，我们回顾了最近的数据，表明单细胞 mRNA-seq 和神经解剖学的结合可以揭示 GABA _{A前所未有的细胞类型和网络特异性}R 亚基并限制亚基构型的排列，从而使 GABA _A R 生理学和药理学合理化。通过比较主要细胞和中间神经元的 RNA-seq 数据，我们讨论了 GABA _A R 亚基分配、GABA 输入来源的多样性以及突触和突触外位点的操作规则之间的紧密匹配。我们建议对所有 GABA _A R 亚基进行同步分析，特别是与特定行为相关的分析，可以克服单个亚基的遗传和药理学操作的现有缺陷。通过使用 α1 和 α5 GABA _AR 亚基，我们将海马空间学习作为一个过程，尽管迄今为止有许多研究可用，但在 GABA _A R 亚型要求方面既不存在共识也不存在因果关系，从而削弱了 GABA 信号突触后编码的统一概念。最后，我们通过受体异聚化、信号转导的交叉调节和变构来解决多巴胺和内源性大麻素对 GABA _{A R 亚基的调节。}总之，本综述中的数据推断，多参数计算获得了提高认知和神经精神疾病中GABA _{A Rs 功能知识的动力。}