Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus
Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus
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DOI：
10.1113/jphysiol.2005.093781
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发表时间：
2006-02-01
影响因子：
5.5
通讯作者：
Magee, JC
中科院分区：
文献类型：
--
作者：
McDermott, CM;Hardy, MN;Magee, JC
虽然睡眠的功能仍然难以捉摸，但有令人信服的证据表明睡眠在学习和记忆中起着重要作用。许多研究表明，睡眠剥夺（SD）会导致海马长时程增强（LTP）功能的显著受损。在这项研究中，我们试图确定这种损害的机制。SD后72小时，使用多平台技术，我们观察到减少的全细胞记录NMDA/AMPA比率的CA 1锥体细胞在响应Schaffer侧支刺激。这种损害是睡眠剥夺所特有的，因为大鼠被放置在一个允许睡眠的大平台上，具有正常的NMDA/AMPA比率。局部应用高渗透压溶液诱发的mEPSC显示AMPA受体功能无差异。从CA 1细胞远端树突切除的外向斑记录的NMDA电流在SD后显示振幅降低。虽然没有改变谷氨酸敏感性，通道开放概率或单通道电导的受体，交联试验表明，NR 1和NR 2A亚基的NMDA受体优先保留在细胞质中SD后，表明SD改变NMDAR表面表达。总之，我们已经确定了一个潜在的机制，SD诱导的LTP损伤。这种突触改变可能是睡眠剥夺后认知缺陷的基础，也可能是未来干预研究的目标。
Although the function of sleep remains elusive, there is compelling evidence to suggest that sleep plays an important role in learning and memory. A number of studies have now shown that sleep deprivation (SD) results in significant impairment of long-term potentiation (LTP) in the hippocampus. In this study, we have attempted to determine the mechanisms responsible for this impairment. After 72 h SD using the multiple-platform technique, we observed a reduction in the whole-cell recorded NMDA/AMPA ratio of CA1 pyramidal cells in response to Schaffer collateral stimulation. This impairment was specific to sleep deprivation as rats placed over a single large platform, which allowed sleep, had a normal NMDA/AMPA ratio. mEPSCs evoked by local application of a high osmolarity solution revealed no differences in the AMPA receptor function. NMDA currents recorded from outside-out patches excised from the distal dendrites of CA1 cells displayed a reduction in amplitude after SD. While there were no alterations in the glutamate sensitivity, channel open probability or the single channel conductance of the receptor, a crosslinking assay demonstrated that the NR1 and NR2A subunits of NMDA receptors were preferentially retained in the cytoplasm after SD, indicating that SD alters NMDAR surface expression. In summary, we have identified a potential mechanism underlying SD-induced LTP impairment. This synaptic alteration may underlie the cognitive deficits seen following sleep deprivation and could represent a target for future intervention studies.