Chuluun Bayarsaikhan, Pittaras Elsa, Hong Hyunseung, Fisher Nathan, Colas Damien, Ruby Norman F, Heller H Craig
Biology Department, 371 Serra Mall, Stanford University, Stanford, CA, 94305-5020, USA.
Neurobiol Sleep Circadian Rhythms. 2020 Feb 16;8:100049. doi: 10.1016/j.nbscr.2020.100049. eCollection 2020 May.
The Ts65Dn mouse is a well-studied model of trisomy 21, Down syndrome. This mouse strain has severe learning disability as measured by several rodent learning tests that depend on hippocampal spatial memory function. Hippocampal long-term potentiation (LTP) is deficient in these mice. Short-term daily treatment with low-dose GABA receptor antagonists rescue spatial learning and LTP in Ts65Dn mice leading to the hypothesis that the learning disability is due to GABAergic over-inhibition of hippocampal circuits. The fact that the GABA receptor antagonists were only effective if delivered during the daily light phase suggested that the source of the excess GABA was controlled directly or indirectly by the circadian system. The central circadian pacemaker of mammals is the suprachiasmatic nucleus (SCN), which is largely a GABAergic nucleus. In this study we investigated whether elimination of the SCN in Ts65Dn mice would restore their ability to form recognition memories as tested by the novel object recognition (NOR) task. Full, but not partial lesions of the SCN of Ts65Dn mice normalized their ability to perform on the NOR test. These results suggest that the circadian system modulates neuroplasticity over the time frame involved in the process of consolidation of recognition memories.
Ts65Dn小鼠是一种经过充分研究的21三体综合征（唐氏综合征）模型。通过几种依赖海马体空间记忆功能的啮齿动物学习测试来衡量，该小鼠品系存在严重的学习障碍。这些小鼠的海马体长期增强效应（LTP）存在缺陷。低剂量GABA受体拮抗剂的短期每日治疗可挽救Ts65Dn小鼠的空间学习能力和LTP，这导致了一种假设，即学习障碍是由于海马体回路的GABA能过度抑制所致。GABA受体拮抗剂仅在每日光照阶段给药时才有效，这一事实表明过量GABA的来源直接或间接受昼夜节律系统控制。哺乳动物的中枢昼夜节律起搏器是视交叉上核（SCN），它在很大程度上是一个GABA能核团。在本研究中，我们调查了消除Ts65Dn小鼠的SCN是否会恢复它们通过新物体识别（NOR）任务测试形成识别记忆的能力。Ts65Dn小鼠SCN的完全而非部分损伤使其在NOR测试中的表现能力恢复正常。这些结果表明，昼夜节律系统在识别记忆巩固过程所涉及的时间框架内调节神经可塑性。
