α7 nicotinic acetylcholine receptors on GABAergic interneurons evoke dendritic and somatic inhibition of hippocampal neurons
α7 nicotinic acetylcholine receptors on GABAergic interneurons evoke dendritic and somatic inhibition of hippocampal neurons
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DOI：
10.1152/jn.00316.2001
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发表时间：
2002-01-01
影响因子：
2.5
通讯作者：
Dunwiddie, TV
中科院分区：
文献类型：
--
作者：
Buhler, AV;Dunwiddie, TV
海马中的GABA能中间神经元表达高水平的α 7烟碱乙酰胆碱受体，但由于海马中间神经元所起的不同作用，这些受体的激活对海马输出神经元的影响（即，CA 1锥体细胞）不清楚。海马中间神经元的激活可以直接抑制锥体神经元的活动，但也可以产生对其他GABA能细胞的抑制，导致锥体细胞的去抑制。为了表征由这些受体激活的抑制回路，将外源性乙酰胆碱直接应用于海马切片中的CA 1中间神经元，并从锥体神经元或中间神经元记录所产生的突触后反应。在27/131个中间神经元/锥体细胞对中观察到GABA（A）受体介导的抑制电流，但未观察到自发抑制事件或GABA（B）受体介导反应的去抑制情况。荷包牡丹碱敏感的GABA（A）受体介导的电流的两个群体可以区分基于他们的动力学和振幅。解剖重建的interneurons在一个子集的连接对支持的假设，这两个群体对应于抑制性突触位于无论是在锥体细胞的胞体或树突。在11 interneuron/interneuron细胞对，一个突触前神经元，观察到产生强抑制电流在几个附近的interneuron，这表明，也可能发生的锥体神经元的去抑制。所有三种类型的抑制反应（体细胞锥体，树突锥体，和interneuronal）被封锁的α 7受体选择性拮抗剂methylylycaconitine。这些数据表明，这些功能不同的电路激活的α 7受体的结果在海马锥体神经元以及中间神经元的显着抑制。
GABAergic interneurons in the hippocampus express high levels of alpha7 nicotinic acetylcholine receptors, but because of the diverse roles played by hippocampal interneurons, the impact of activation of these receptors on hippocampal output neurons (i.e., CA1 pyramidal cells) is unclear. Activation of hippocampal interneurons could directly inhibit pyramidal neuron activity but could also produce inhibition of other GABAergic cells leading to disinhibition of pyramidal cells. To characterize the inhibitory circuits activated by these receptors, exogenous acetylcholine was applied directly to CA1 interneurons in hippocampal slices, and the resulting postsynaptic responses were recorded from pyramidal neurons or interneurons. Inhibitory currents mediated by GABA(A) receptors were observed in 27/131 interneuron/pyramidal cell pairs, but no instances of disinhibition of spontaneous inhibitory events or GABA(B) receptor-mediated responses were observed. Two populations of bicuculline-sensitive GABA(A) receptor-mediated currents could be distinguished based on their kinetics and amplitude. Anatomical reconstructions of the interneurons in a subset of connected pairs support the hypothesis that these two populations correspond to inhibitory synapses located either on the somata or dendrites of pyramidal cells. In 11 interneuron/interneuron cell pairs, one presynaptic neuron was observed that produced strong inhibitory currents in several nearby interneurons, suggesting that disinhibition of pyramidal neurons may also occur. All three types of inhibitory responses (somatic-pyramidal, dendritic-pyramidal, and interneuronal) were blocked by the alpha7 receptor-selective antagonist methyllycaconitine. These data suggest activation of these functionally distinct circuits by alpha7 receptors results in significant inhibition of both hippocampal pyramidal neurons as well as interneurons.