Past studies find that chronic stress alters inhibitory, GABAergic circuitry of neurons in distinct hippocampal subregions. Less clear is whether these effects persist weeks after chronic stress ends, and whether these effects involve changes in the total number of hippocampal GABAergic neurons or modulates the function of specific GABAergic subtypes. A transgenic mouse line (VGAT:Cre Ai9) containing an indelible marker for GABAergic neurons (tdTomato) throughout the brain was used to determine whether chronic stress alters total GABAergic neuronal number or the expression of two key GABAergic cell subtypes, calretinin expressing (CR+) and somatostatin expressing (SOM+) neurons, and whether these changes endure weeks later. Male and female mice were chronically stressed in wire mesh restrainers for 6h/d/21d (Str) or not (Con), and then allowed a 3 week rest period (Str‐Rest) and compared to those without a rest period (Str‐NoRest). Epifluorescent microscope images of immunohistochemistry‐processed brains were quantified to estimate the total number of fluorescently‐labeled hippocampal GABAergic neurons and the proportion that were CR+ or SOM+. Neither chronic stress nor sex altered the total number of GABAergic cells. In contrast, chronic stress reduced the expression of CR+ in the CA3 region of the hippocampus in both males and females, with robust reductions in the DG region of males, but not females, and these changes reversed following a rest period. Chronic stress also reduced the proportion of hippocampal SOM+ neurons and this reduction persisted even with a rest period. These results show chronic stress dynamically reduced CR expression without changing total inhibitory neuronal number and point to CR as a potential new lead to understand mechanisms by which chronic stress alters hippocampal function.

中文翻译：

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慢性应激对海马钙结合蛋白和生长抑素阳性细胞有不同的即时和延迟影响

过去的研究发现，慢性压力会改变不同海马亚区域神经元的抑制性 GABA 能回路。不太清楚的是，这些影响是否会在慢性压力结束后持续数周，以及这些影响是否涉及海马 GABA 能神经元总数的变化或调节特定 GABA 能亚型的功能。转基因小鼠品系 ( VGAT:Cre Ai9 ) 在整个大脑中含有不可磨灭的 GABA 能神经元 (tdTomato) 标记，用于确定慢性应激是否会改变 GABA 能神经元总数或两种关键 GABA 能细胞亚型的表达，钙视网膜蛋白表达 (CR+)和表达生长抑素（SOM+）的神经元，以及这些变化是否会在几周后持续。雄性和雌性小鼠在金属丝网限制器中长期受压 6 小时/天/21 天（Str）或不承受（Con），然后给予 3 周的休息期（Str-Rest），并与没有休息期的小鼠（Str-Rest）进行比较。没有休息）。对免疫组织化学处理的大脑的落射荧光显微镜图像进行量化，以估计荧光标记的海马 GABA 能神经元的总数以及 CR+ 或 SOM+ 的比例。慢性压力和性别都不会改变 GABA 能细胞的总数。相比之下，慢性压力会降低男性和女性海马 CA3 区 CR+ 的表达，其中男性 DG 区大幅减少，但女性则不然，而且这些变化在休息一段时间后会逆转。慢性压力还减少了海马 SOM+ 神经元的比例，而且这种减少即使在休息期间也会持续存在。这些结果表明，慢性应激动态降低 CR 表达，而不改变总抑制性神经元数量，并指出 CR 是了解慢性应激改变海马功能机制的潜在新线索。