Nicotinic receptors on local circuit neurons in dentate gyrus: A potential role in regulation of granule cell excitability
Nicotinic receptors on local circuit neurons in dentate gyrus: A potential role in regulation of granule cell excitability
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DOI：
10.1152/jn.01036.2002
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发表时间：
2003-06-01
影响因子：
2.5
通讯作者：
Papke, RL
中科院分区：
文献类型：
--
作者：
Frazier, CJ;Strowbridge, BW;Papke, RL
虽然齿状回是隔-海马胆碱能传入的主要靶点之一，但对该地区神经元的胆碱能生理学知之甚少。通过全细胞膜片钳记录和在水平切片上局部短暂应用外源性激动剂，我们发现含α7烟碱型乙酰胆碱受体(NAChRs)的功能性体细胞在分子层中间神经元、门区中间神经元和齿状脑门区的谷氨酸能苔藓细胞上有较强的表达。相反，在阿托品存在的情况下，齿状回的主要神经元，即颗粒细胞，通常对局部的体细胞或树突应用ACh没有反应。我们还证明，胆碱能激活门下颗粒间神经元上含有α7的nAChRs可以在附近的颗粒细胞产生甲基鸟苷敏感的GABA能抑制性突触后电流(IPSCs)，并增强电刺激的单突触IPSC的幅度。此外，颗粒下神经元上含有α7的nAChRs的激活与谷氨酸在这些细胞上的突触释放相一致，将加强颗粒细胞的功能抑制。这些结果提示，来自内嗅皮层的谷氨酸能传入和来自内侧隔区的胆碱能传入之间的复杂相互作用可能参与了颗粒细胞功能的正常调节。这两条传入通路之间的这种关系可能与年龄相关的记忆功能障碍和涉及兴奋性调节的障碍(如颞叶癫痫)的研究高度相关。
Although the dentate gyrus is one of the primary targets of septo-hippocampal cholinergic afferents, relatively little is known about the cholinergic physiology of neurons in the area. By combining whole cell patch-clamp recording with brief local application of exogenous agonists in horizontal slices, we found that there is robust expression of functional somatic alpha7-containing nicotinic acetylcholine receptors (nAChRs) on molecular layer interneurons, hilar interneurons, and the glutamatergic mossy cells of the dentate hilus. In contrast, the principal neurons of the dentate gyrus, the granule cells, are generally unresponsive to focal somatic or dendritic application of ACh in the presence of atropine. We also demonstrate that cholinergic activation of alpha7-containing nAChRs on the subgranular interneurons of the hilus can produce methyllycaconitine-sensitive GABAergic inhibitory postsynaptic currents (IPSCs) in nearby granule cells and enhance the amplitude of an electrically evoked monosynaptic IPSC. Further, activation of alpha7-containing nAChRs on subgranular interneurons that is timed to coincide with synaptic release of glutamate onto these cells will enhance the functional inhibition of granule cells. These findings suggest that a complex interplay between glutamatergic afferents from the entorhinal cortex and cholinergic afferents from the medial septum could be involved in the normal regulation of granule cell function. Such a relationship between these two afferent pathways could be highly relevant to the study of both age-related memory dysfunction and disorders involving regulation of excitability, such as temporal lobe epilepsy.