Numerous aging studies have identified a shift in the excitatory/inhibitory (E/I) balance with heightened hippocampal neural activity associated with age-related memory impairment across species, including rats, monkeys, and humans. Neurobiological investigations directed at the hippocampal formation have demonstrated that unimpaired aged rats performing on par with young adult rats in a spatial memory task exhibit gene expression profiles, mechanisms for plasticity, and altered circuit/network function, which are distinct from younger rats. Particularly striking is a convergence of observational evidence that aged unimpaired rats augment recruitment of mechanisms associated with neural inhibition, a finding that may represent an adaptive homeostatic adjustment necessary to maintain neural plasticity and memory function in aging. In this study, we test the effect of limiting inhibition via administration of TB21007, a negative allosteric modulator of the alpha 5 subtype of gamma-aminobutyric acid type A α5 receptor, on a radial arm maze assessment of memory function. Impaired memory performance produced by this intervention in otherwise high-performing aged rats supports an adaptive role for gamma-aminobutyric acid in the functional maintenance of intact cognition in aging.

中文翻译：

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具有保留认知的衰老中抑制性募集的意义：限制 GABAA α5 功能会产生记忆障碍

许多衰老研究已经确定了兴奋/抑制 (E/I) 平衡的变化，海马神经活动增强，与年龄相关的记忆障碍有关，包括大鼠、猴子和人类。针对海马形成的神经生物学研究表明，未受损的老年大鼠在空间记忆任务中表现出与年轻成年大鼠相当的基因表达谱、可塑性机制和改变的电路/网络功能，这与年轻大鼠不同。特别引人注目的是观察性证据的融合，即老年未受损大鼠增加了与神经抑制相关的机制的募集，这一发现可能代表了在衰老过程中维持神经可塑性和记忆功能所必需的适应性稳态调整。在这项研究中，我们测试了通过施用 TB21007（一种 γ-氨基丁酸 A 型 α5 受体的 α 5 亚型的负变构调节剂）限制抑制对记忆功能的径向臂迷宫评估的影响。这种干预在其他方面表现出色的老年大鼠中产生的记忆力受损支持 γ-氨基丁酸在衰老过程中完整认知的功能维持中的适应性作用。