Synaptic activation of mGluR1 generates persistent depression of a fast after-depolarizing potential in CA3 pyramidal neurons
Synaptic activation of mGluR1 generates persistent depression of a fast after-depolarizing potential in CA3 pyramidal neurons
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DOI：
10.1111/j.1460-9568.2010.07565.x
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发表时间：
2011-03-01
影响因子：
3.4
通讯作者：
Randall, Andrew D.
中科院分区：
文献类型：
--
作者：
Brown, Jon T.;Booth, Clair A.;Randall, Andrew D.
突发放电是海马锥体神经元的一个重要特性。I组代谢型谷氨酸受体（mGluRs）对神经元的突触和内在特性产生多种影响。我们研究了这些受体的短暂激活是否会导致大鼠海马CA3锥体细胞（CA3- pcs）固有兴奋性的持续改变。在全细胞电流钳记录中，由滤波的伪随机噪声组成的电流刺激产生的动作电位放电的平均频率类似于1.5-2 Hz。对脉冲间隔的分析表明，这种放电包括高频（100赫兹）爆发活动的重要组成部分（约20%）。用(S)-3,5-二羟基苯基甘氨酸[(S)-DHPG]激活I组mGluRs选择性地消除了高频脉冲，在(S)-DHPG洗脱后，这种效果持续了30分钟。CA3-PCs的快速去极化电位（ADP）是产生高频动作电位爆发的重要因素。在短时间应用(S)-DHPG后，ADP持续下降。这种作用被mGluR1拮抗剂(S)-(+)- α -氨基-4-羧基-2-甲基苯乙酸（LY367385）阻断。相反，抑制对mGluR5拮抗剂2-甲基-6-（苯乙炔基）吡啶盐酸盐（MPEP）和α -氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)/kainate， n -甲基-d-天冬氨酸（NMDA）和γ -氨基丁酸（GABA）(A)拮抗剂具有抗性。与其他在CA3-PCs中产生持续抑制ADP的操作不同，dhpg介导的ADP抑制对Kv7通道抑制剂10,10-双（4-吡啶基甲基）-9(10H)-蒽酮二盐酸（XE991）和1,2-双（2-氨基苯氧基）乙烷-N，N，N‘，N’-四乙酸（BAPTA）的强细胞内Ca2+缓冲不敏感。mGluRs在联合-联合通路上的突触激活也导致突触后CA3-PCs中ADP的持续下降，这一过程被LY367385阻断。这些数据首次证明mGluR1的突触激活可以调节海马神经元的固有兴奋性。
Burst firing is an important property of hippocampal pyramidal neurons. Group I metabotropic glutamate receptors (mGluRs) produce a multitude of effects on both the synaptic and intrinsic properties of neurons. We investigated whether brief activation of these receptors results in persistent modifications to the intrinsic excitability of rat hippocampal CA3 pyramidal cells (CA3-PCs). In whole-cell current-clamp recordings, current stimuli consisting of filtered, pseudo-random noise produced action potential firing with a mean frequency of similar to 1.5-2 Hz. Analysis of spike intervals revealed that this firing included a substantial component (similar to 20%) of high-frequency (similar to 100 Hz) bursting activity. Activation of group I mGluRs with (S)-3,5-dihydroxyphenylglycine [(S)-DHPG] selectively eliminated the high-frequency bursts, an effect that persisted > 30 min after (S)-DHPG washout. The fast after-depolarizing potential (ADP) of CA3-PCs is known to be important for generating high-frequency action potential bursting. This ADP was persistently depressed following a short application of (S)-DHPG. This effect was blocked by the mGluR1 antagonist, (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385). In contrast, the depression was resistant to the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate, N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid (GABA)(A) antagonists. Unlike other manipulations that generate persistent depression of the ADP in CA3-PCs, DHPG-mediated ADP depression was insensitive to the Kv7 channel inhibitor 10,10-bis(4-Pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and strong intracellular Ca2+ buffering by 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Synaptic activation of mGluRs in the associational-commissural pathway also resulted in persistent depression of the ADP in postsynaptic CA3-PCs, which was blocked by LY367385. These data represent the first evidence that synaptic activation of mGluR1 can modulate the intrinsic excitability properties of hippocampal neurons.