Suprachiasmatic lesions restore object recognition in down syndrome model mice
Suprachiasmatic lesions restore object recognition in down syndrome model mice
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DOI：
10.1016/j.nbscr.2020.100049
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发表时间：
2020-05-01
影响因子：
--
通讯作者：
Heller, H. Craig
中科院分区：
文献类型：
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作者：
Chuluun, Bayarsaikhan;Pittaras, Elsa;Heller, H. Craig
Ts65Dn小鼠是21三体唐氏综合征的充分研究模型。这种小鼠品系具有严重的学习障碍，如通过依赖于海马空间记忆功能的几种啮齿动物学习测试所测量的。海马长时程增强（LTP）在这些小鼠中是缺乏的。低剂量GABA受体拮抗剂的短期每日治疗挽救Ts65Dn小鼠的空间学习和LTP，导致学习障碍是由于海马回路的GABA能过度抑制的假设。GABA受体拮抗剂只有在每日光照阶段递送才有效，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。哺乳动物的中心昼夜节律起搏器是视交叉上核（SCN），其主要是GABA能核。在这项研究中，我们研究了消除Ts65Dn小鼠的SCN是否会恢复其形成识别记忆的能力，如通过新物体识别（NOR）任务所测试的。Ts65Dn小鼠的SCN的完全而非部分损伤使其进行NOR测试的能力正常化。这些结果表明，昼夜节律系统调节神经可塑性的时间范围内参与巩固的过程中识别记忆。
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.