Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, Massachusetts 02478, USA.
Stress Neurobiology Laboratory, McLean Hospital, Belmont, Massachusetts 02478, USA.
Learn Mem. 2020 Sep 15;27(10):423-428. doi: 10.1101/lm.052084.120. Print 2020 Oct.
Reduction in the expression or function of α5-subunit-containing GABA receptors (α5GABARs) leads to improvement in several hippocampus-dependent memory domains. However, studies thus far mostly lack anatomical specificity in terms of neuronal circuits and populations. We demonstrate that mice with a selective knockdown of α5GABARs in CA1 pyramidal neurons (α5CA1KO mice) show improved spatial and trace fear-conditioning memory. Unexpectedly, α5CA1KO mice were comparable to controls in contextual fear-conditioning but showed an impairment in context discrimination, suggesting fine-tuning of activity in CA1 pyramidal cell dendrites through α5-mediated inhibition might be necessary for distinguishing highly similar contexts.
减少 α5 亚基 GABA 受体（α5GABARs）的表达或功能可改善几种海马依赖的记忆领域。然而，迄今为止的研究在神经元回路和群体方面缺乏解剖学特异性。我们证明，在 CA1 锥体神经元中选择性敲低 α5GABARs 的小鼠（α5CA1KO 小鼠）显示出空间和痕迹恐惧条件记忆的改善。出乎意料的是，α5CA1KO 小鼠在情境恐惧条件下与对照小鼠相当，但在情境辨别方面存在障碍，这表明通过 α5 介导的抑制来精细调节 CA1 锥体神经元树突的活动可能对于区分高度相似的情境是必要的。
