Hippocampal CA3 NMDA receptors are crucial for adaptive timing of trace eyeblink conditioned response
Hippocampal CA3 NMDA receptors are crucial for adaptive timing of trace eyeblink conditioned response
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DOI：
10.1523/jneurosci.4142-05.2006
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
Kano, M
中科院分区：
文献类型：
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作者：
Kishimoto, Y;Nakazawa, K;Kano, M
眨眼反射的经典条件反射是运动反应的联想学习的一种简单形式。为了研究海马CA 3 NMDA受体（NR）在非空间联想记忆中的参与，对成年CA 3锥体细胞中选择性缺乏NR 1亚基的小鼠[CA 3-NR 1敲除（KO）小鼠]进行眨眼条件反射。小鼠接受成对呈现的听觉条件刺激（CS）和眶周休克非条件刺激（US）。随着CS的重复呈现，随后是US，野生型小鼠学会了在US发作之前预期其眨眼。我们首先证实，野生型小鼠需要一个完整的海马体中的痕迹版本的眨眼条件，其中CS和US不重叠，创造一个无刺激的时间间隔为500毫秒。在相同的条件下，CA 3-NR 1基因敲除小鼠成功地收购条件反射（CR）在10天的收购会议，而CR的灭绝受损的第一天灭绝会议。重要的是，CA 3-NR 1 KO小鼠在每日采集期的前五次试验期间，适应性定时CR的形成受损。根据CR消退受损，在消退期也观察到CR时间异常。这些结果表明，CA 3-NR 1基因敲除小鼠不能快速检索自适应CR时间，这表明CA 3 NR在痕迹条件反射的自适应CR时间记忆中起着至关重要的作用。
Classical conditioning of the eyeblink reflex is a simple form of associative learning for motor responses. To examine the involvement of hippocampal CA3 NMDA receptors (NRs) in nonspatial associative memory, mice lacking an NR1 subunit selectively in adult CA3 pyramidal cells [CA3-NR1 knock-out (KO) mice] were subjected to eyeblink conditioning paradigms. Mice received paired presentations of an auditory conditioned stimulus (CS) and a periorbital shock unconditioned stimulus (US). With repeated presentation of the CS followed by the US, wild-type mice learned to blink in anticipation of the US before its onset. We first confirmed that wild-type mice require an intact hippocampus in the trace version of eyeblink conditioning in which the CS and US do not overlap, creating a stimulus-free time gap of 500 ms. Under the same condition, CA3-NR1 KO mice successfully acquired conditioned responses (CRs) during the 10 d acquisition sessions, whereas the extinction of CRs was impaired on the first day of extinction sessions. Importantly, CA3-NR1 KO mice were impaired in the formation of an adaptively timed CR during the first five trials in the daily acquisition sessions. The aberrantly timed CR was also observed in the extinction sessions in accordance with the impaired extinction of CRs. These results indicate that CA3-NR1 KO mice are unable to rapidly retrieve adaptive CR timing, suggesting that CA3 NRs play a crucial role in the memory of adaptive CR timing in trace conditioning.