α2 Nicotine receptors function as a molecular switch to continuously excite a subset of interneurons in rat hippocampal circuits
α2 Nicotine receptors function as a molecular switch to continuously excite a subset of interneurons in rat hippocampal circuits
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DOI：
10.1111/j.1460-9568.2009.06706.x
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发表时间：
2009-04-01
影响因子：
3.4
通讯作者：
Sumikawa, Katumi
中科院分区：
文献类型：
--
作者：
Jia, Yousheng;Yamazaki, Yoshihiko;Sumikawa, Katumi
在海马不同的解剖和细胞位置的烟碱乙酰胆碱受体（nAChRs）的快速激活差异调制海马电路的操作。然而，尼古丁的持续存在如何影响海马回路的正常运作在很大程度上是未知的。在这里，我们使用单细胞和双细胞全细胞记录来解决这个问题。我们发现，水平取向的中间神经元在层oriens/肺泡连续放电的尼古丁的存在下的动作电位。在这些中间神经元中，浴用尼古丁产生缓慢的内向电流，该电流被非α 7拮抗剂二氢-β-赤藓定很好地维持和抑制。单细胞逆转录-聚合酶链反应分析表明，尼古丁反应的中间神经元始终积极的α 2亚基mRNA。这些观察结果表明，在尼古丁的存在下，由于α 2* nAChR的持续激活，定向层/肺泡中的中间神经元的子集持续兴奋。这些中间神经元突触连接到锥体细胞，尼古丁增加抑制性基线电流在突触和抑制相位抑制在相同的突触。尼古丁诱导的抑制活性增加了背景噪声和掩蔽小阶段性抑制锥体细胞，起源于其他interneurons在放射层。因此，尼古丁的持续存在通过激活不同中间神经元群体上的非脱敏α 2 nAChR亚型来门控抑制回路，从而改变海马回路的正常操作。
Rapid activation of nicotinic acetylcholine receptors (nAChRs) at various anatomical and cellular locations in the hippocampus differentially modulates the operation of hippocampal circuits. However, it is largely unknown how the continued presence of nicotine affects the normal operation of hippocampal circuits. Here, we used single and dual whole-cell recordings to address this question. We found that horizontally oriented interneurons in the stratum oriens/alveus continuously discharged action potentials in the presence of nicotine. In these interneurons, bath application of nicotine produced slow inward currents that were well maintained and inhibited by the non-alpha 7 antagonist dihydro-beta-erythroidine. Single-cell reverse transcription-polymerase chain reaction analysis showed that nicotine-responding interneurons were consistently positive for the alpha 2 subunit mRNA. These observations suggest that in the presence of nicotine, a subset of interneurons in the stratum oriens/alveus are continuously excited due to the sustained activation of alpha 2* nAChRs. These interneurons were synaptically connected to pyramidal cells, and nicotine increased inhibitory baseline currents at the synapses and suppressed phasic inhibition at the same synapses. Nicotine-induced inhibitory activity increased background noise and masked small phasic inhibition in pyramidal cells, originating from other interneurons in the stratum radiatum. Thus, the continued presence of nicotine alters the normal operation of hippocampal circuits by gating inhibitory circuits through activating a non-desensitizing alpha 2 nAChR subtype on a distinct population of interneurons.