Cobb S R, Larkman P M, Bulters D O, Oliver L, Gill C H, Davies C H
Division of Neuroscience and Biomedical Systems, University of Glasgow, Glasgow, G12 8QQ, UK.
Neuropharmacology. 2003 Mar;44(3):293-303. doi: 10.1016/s0028-3908(02)00405-7.
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.
海马体CA3区的神经元网络在代谢型谷氨酸受体（mGluRs）或毒蕈碱型乙酰胆碱受体（mAChRs）激活时会产生刻板的电活动模式，这些模式由间歇性的长时间振荡活动组成。鉴于此类网络反应的动力学较慢，我们研究了超极化激活内向电流（I(h)）在海马体振荡状态的产生和维持中可能发挥的作用。在海马体“微型切片”实验中，通过切断连接传入神经来分离海马体的主要亚区，结果显示CA3区是mGluR和mAChR介导的网络反应的主要产生部位。随后的膜片钳实验证实，CA3区的主要细胞中存在一种对氯化铯和选择性I(h)阻滞剂ZD-7288敏感的显著超极化激活内向电流。此外，在存在mAChR或mGluR激动剂的情况下，这些细胞表现出一种与AMPA受体介导的突触传递无关的缓慢膜电位振荡。阻断I(h)会抑制这种振荡以及mGluR和mAChR诱导的基于θ波的间歇性网络振荡行为。这些数据支持了I(h)起搏电流在海马体中模式化神经元活动的产生中很重要这一观点。
