Activation of Ih is necessary for patterning of mGluR and mAChR induced network activity in the hippocampal CA3 region
Activation of Ih is necessary for patterning of mGluR and mAChR induced network activity in the hippocampal CA3 region
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DOI：
10.1016/s0028-3908(02)00405-7
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发表时间：
2003-03-01
影响因子：
4.7
通讯作者：
Davies, CH
中科院分区：
文献类型：
--
作者：
Cobb, SR;Larkman, PM;Davies, CH
代谢型谷氨酸受体(MGluRs)或M胆碱型乙酰胆碱受体(MAChRs)激活后，海马CA3区神经元网络产生陈旧的电活动模式，后者由间歇性长时间振荡活动组成。鉴于这种网络反应的缓慢动力学，我们研究了超极化激活的内向电流(I-h)在海马振荡状态的产生和维持中的可能贡献。海马区“迷你切片”实验表明，CA3区是mGluR和mAChR介导的网络反应的主要产生区。随后的膜片钳实验证实，在CA3区的主细胞上存在显著的超极化激活的内向电流，该电流对氯化铯和选择性的I-h阻断剂ZD-7288敏感。此外，在mAChR或mGluR激动剂的存在下，这些细胞表现出不依赖于AMPA受体介导的突触传递的慢性膜电位振荡。阻断i-h可抑制这种振荡以及mGluR和mAChR诱导的基于theta的间歇性网络振荡行为。这些数据支持这样一种观点，即i-h起搏器电流在海马神经元活动模式的产生中起重要作用。(C)2003爱思唯尔科学有限公司。保留所有权利。
Neuronal networks of the hippocampal CA3 region generate stereotyped patterns of electrical activity in response to activation of metabotropic glutamate receptors (mGluRs) or muscarinic acetylcholine receptors (mAChRs) that consist of intermittent episodes of prolonged oscillatory activity. In light of the slow kinetics of such network responses, we investigated the possible contribution of the hyperpolarisation-activated inward current (I-h) in the generation and maintenance of hippocampal oscillatory states. Hippocampal 'mini-slice' experiments in which the main subfields of the hippocampus were isolated by transection of the connecting afferents revealed that the CA3 region was the primary generator of both mGluR and mAChR-mediated network responses. Subsequent patch-clamp experiments confirmed the presence of a prominent hyperpolarisation-activated inward current in the principal cells of the CA3 region that was sensitive to caesium chloride and the selective I-h blocker ZD-7288.Furthermore, in the presence of mAChR or mGluR agonists these cells exhibited a slow membrane potential oscillation that was independent of AMPA receptor-mediated synaptic transmission. Blockade of I-h suppressed this oscillation as well as mGluR and mAChR-induced theta based intermittent network oscillatory behaviour. These data support the idea that the I-h pacemaker current is important in the generation of patterned neuronal activities in the hippocampus. (C) 2003 Elsevier Science Ltd. All rights reserved.