Functional nicotinic ACh receptors on interneurones in the rat hippocampus

Functional nicotinic ACh receptors on interneurones in the rat hippocampus
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DOI:
10.1111/j.1469-7793.1997.603bd.x
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发表时间:
1997-11-01
影响因子:
5.5
通讯作者:
Yakel, JL
Yakel, JL
中科院分区:
医学1区
文献类型:
--
作者:
Jones, S;Yakel, JL

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1.采用全细胞膜片钳技术研究大鼠海马脑片烟碱型乙酰胆碱受体(nAChRs). ACh(100 μ M)的反应被检测到抑制interneurones在CA 1领域的海马适当的和在齿状回,但不是在任何一个区域的主要兴奋性神经元。根据神经元的形态和位置,对不同的神经元类型进行鉴定.电流钳记录显示乙酰胆碱兴奋海马和齿状回的中间神经元。在电压钳记录,乙酰胆碱激活的内向电流记录从interneurons的存在下,阻断剂的突触传递和毒蕈碱乙酰胆碱受体拮抗剂阿托品。该响应ACh的零电流电位接近0 mV。4.乙酰胆碱的作用被nAChR-选择性激动剂尼古丁(100 μ M)和1,1-二甲基-4-苯基-哌嗪碘化物(DMPP,100 μ M)模拟。ACh的反应可逆地拮抗神经元nAChR拮抗剂美加明(10 μ M)。nAChR α 7亚基选择性拮抗剂α-银环蛇毒素(100 nM)和甲基牛乌头碱(10 nM)也可抑制对乙酰胆碱的反应。这些观察结果表明在大鼠海马中抑制性中间神经元上存在功能性nAChR。因此,一个新的机制,乙酰胆碱可以调节海马神经元的活动被揭示。
1. Neuronal nicotinic ACh receptors (nAChRs) were studied in the rat hippocampal slice preparation using whole-cell patch-clamp recording techniques.2. Responses to ACh (100 mu M) were detected on inhibitory interneurones in the CA1 field of the hippocampus proper and in the dentate gyrus, but not on principal excitatory neurones in either region. The different neuronal types were identified based on their morphology and location.3. ACh excited interneurones in the hippocampus and dentate gyrus in current-clamp recordings. In voltage-clamp recordings, ACh-activated inward currents were recorded from interneurones in the presence of blockers of synaptic transmission and the muscarinic ACh receptor antagonist atropine. The zero current potential for this response to ACh was near 0 mV.4. The effect of ACh was mimicked by the nAChR-selective agonists nicotine (100 mu M) and 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP, 100 mu M). The response to ACh was reversibly antagonized by the neuronal nAChR antagonist mecamylamine (10 mu M). The nAChR alpha 7 subunit-selective antagonists alpha-bungarotoxin (100 nM) and methyllycaconitine (10 nM) also inhibited the response to ACh.5. These observations demonstrate the presence of functional nAChRs on inhibitory interneurones in the rat hippocampus. Thus, a novel mechanism by which ACh can regulate neuronal activity in the hippocampus is revealed.