Table_5_Differential expression of GABAA receptor subunits δ and α6 mediates tonic inhibition in parvalbumin and somatostatin interneurons in the mouse hippocampus.xlsx

Inhibitory γ-aminobutyric acid (GABA)-ergic interneurons mediate inhibition in neuronal circuitry and support normal brain function. Consequently, dysregulation of inhibition is implicated in various brain disorders. Parvalbumin (PV) and somatostatin (SST) interneurons, the two major types of GABAergic inhibitory interneurons in the hippocampus, exhibit distinct morpho-physiological properties and coordinate information processing and memory formation. However, the molecular mechanisms underlying the specialized properties of PV and SST interneurons remain unclear. This study aimed to compare the transcriptomic differences between these two classes of interneurons in the hippocampus using the ribosome tagging approach. The results revealed distinct expressions of genes such as voltage-gated ion channels and GABAA receptor subunits between PV and SST interneurons. Gabrd and Gabra6 were identified as contributors to the contrasting tonic GABAergic inhibition observed in PV and SST interneurons. Moreover, some of the differentially expressed genes were associated with schizophrenia and epilepsy. In conclusion, our results provide molecular insights into the distinct roles of PV and SST interneurons in health and disease.

抑制性γ-氨基丁酸（γ-aminobutyric acid，GABA）能中间神经元介导神经元环路中的抑制作用并维持正常脑功能。因此，抑制功能失调与多种脑部疾病密切相关。小白蛋白（Parvalbumin，PV）和生长抑素（Somatostatin，SST）中间神经元是海马脑区中两类主要的GABA能抑制性中间神经元，它们具有独特的形态生理特性，并协同参与信息处理与记忆形成过程。然而，PV与SST中间神经元的特化特性背后的分子机制仍不明晰。本研究旨在通过核糖体标签技术对比海马内这两类中间神经元的转录组差异。研究结果显示，PV与SST中间神经元在电压门控离子通道、GABAA受体（GABAA receptor）亚基等基因的表达上存在显著差异。Gabrd与Gabra6被证实是导致PV与SST中间神经元之间张力性GABA能抑制作用差异的关键因子。此外，部分差异表达基因与精神分裂症和癫痫存在关联。综上，本研究结果为PV与SST中间神经元在健康与疾病状态下的独特功能提供了分子层面的见解。