Inhibition and disinhibition of pyramidal neurons by activation of nicotinic receptors on hippocampal interneurons
Inhibition and disinhibition of pyramidal neurons by activation of nicotinic receptors on hippocampal interneurons
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DOI：
10.1152/jn.2000.83.5.2682
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发表时间：
2000-05-01
影响因子：
2.5
通讯作者：
Dani, JA
中科院分区：
文献类型：
--
作者：
Ji, DY;Dani, JA
烟碱型乙酰胆碱受体(NAChRs)在海马区表达，其功能作用已开始被研究。本文研究了激活nAChR对大鼠海马脑片CA1区中间神经元和锥体神经元活动的影响。在M受体被抑制的CA1层，局部加压乙酰胆碱(ACh)可引起82%的神经元产生烟碱电流。大多数ACh诱发的电流对甲基乌头碱敏感，它是一种含有α7的nAChRs的特异性抑制剂。非特异性nAChR抑制剂也检测到甲基乌头碱不敏感的烟碱电流。根据这些神经元的电生理特性，确定其为GABA能中间神经元。加压ACh可在约70%的中间神经元诱发动作电位的放电。ACh诱导的中间神经元兴奋可引起锥体神经元的抑制或解除抑制。这种抑制是从锥体神经元记录的，表现为GABA能突触活动的爆发。这种突触活动对荷包牡丹碱敏感，表明GABA(A)受体介导了ACh诱导的突触电流。当ACh注射到中间神经元上时，这种去抑制从锥体神经元记录为自发的GABA能突触活动的减少。这种抑制和去抑制对甲基乌头碱和甲氨基甲胺都很敏感，说明这种作用需要激活中间神经元上的烟碱受体。这些结果表明，nAChRs能够通过兴奋中间神经元，从而抑制或解除对锥体神经元的抑制，来调节海马神经元的回路。
Nicotinic acetylcholine receptors (nAChRs) are expressed in the hippocampus, and their functional roles are beginning to be delineated. The effect of nAChR activation on the activity of both interneurons and pyramidal neurons in the CA1 region was studied in rat hippocampal slices, in CA1 stratum radiatum with muscarinic receptors inhibited, local pressure application of acetylcholine (ACh) elicited a nicotinic current in 82% of the neurons. The majority of the ACh-induced currents were sensitive to methyllycaconitine, which is a specific inhibitor of alpha 7-containing nAChRs. Methyllycaconitine-insensitive nicotinic currents also were present as detected by a nonspecific nAChR inhibitor. The ACh-sensitive neurons in the s. radiatum were identified as GABAergic interneurons by their electrophysiological properties. Pressure application of ACh induced firing of action potentials in similar to 70% of the interneurons. The ACh-induced excitation of interneurons could induce either inhibition or disinhibition of pyramidal neurons. The inhibition was recorded from the pyramidal neuron as a burst of GABAergic synaptic activity. That synaptic activity was sensitive to bicuculline, indicating that GABA(A) receptors mediated the ACh-induced synaptic currents. The disinhibition was recorded from the pyramidal neuron as a reduction of spontaneous GABAergic synaptic activity when ACh was delivered onto an interneuron. Both the inhibition and disinhibition were sensitive to either methyllycaconitine or mecamylamine, indicating that activation of nicotinic receptors on interneurons was necessary for the effects. These results show that nAChRs are capable of regulating hippocampal circuits by exciting interneurons and, subsequently, inhibiting or disinhibiting pyramidal neurons.