Pharmacological antagonism of metabotropic glutamate receptor 1 regulates long-term potentiation and spatial reference memory in the dentate gyrus of freely moving rats via N-methyl-D-aspartate and metabotropic glutamate receptor-dependent mechanisms
Pharmacological antagonism of metabotropic glutamate receptor 1 regulates long-term potentiation and spatial reference memory in the dentate gyrus of freely moving rats via N-methyl-D-aspartate and metabotropic glutamate receptor-dependent mechanisms
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DOI：
10.1111/j.1460-9568.2005.03864.x
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发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Manahan-Vaughan, D
中科院分区：
文献类型：
--
作者：
Naie, K;Manahan-Vaughan, D
I组代谢型谷氨酸受体（mGluRs）是体内多种形式的海马突触可塑性所必需的。受体亚型mGluR 1在长时程增强（LTP）和学习中的作用尚不清楚。我们使用选择性拮抗剂（S）-（+）-α-氨基-4-羧基-2-甲苯-乙酸（LY 367385）检测了mGluR 1对海马LTP和空间学习的贡献。雄性Wistar大鼠长期植入记录和刺激电极，使内侧穿通路径齿状回颗粒细胞突触的诱发电位的测量。将注射套管插入同侧脑室，以使药物应用。实验在植入程序后10天开始。我们诱导了一个强大的LTP，持续超过25小时，200赫兹强直。在所有研究浓度下注射LY 367385（在5-穆尔注射体积中4-32 nmol）不影响基础突触传递。相反，我们观察到LTP表达的剂量依赖性损伤：LY 367385（4 nmol）对LTP诱导没有影响，而8和16 nmol LY 367385降低LTP诱导和表达，表明与N-甲基-D-天冬氨酸受体的相互作用。我们评估了每天应用LY 367385（8 nmol）对八臂径向迷宫中性能的影响。与溶剂给药对照组相比，LY 367385给药大鼠显示参考记忆功能缺陷，但未显示工作记忆功能缺陷。饲养、梳理和运动活动不受LY 367385影响。这些数据表明mGluR 1在LTP和学习中的重要作用，并突出了这种mGluR亚型对参考记忆的特殊意义。
Group I metabotropic glutamate receptors (mGluRs) are critically required for multiple forms of hippocampal synaptic plasticity in vivo. The role of the receptor subtype mGluR1 in long-term potentiation (LTP) and learning is unclear. We examined the contribution of mGluR1 to hippocampal LTP and spatial learning using the selective antagonist (S)-(+)-alpha-amino-4carboxy-2-methylbenzene-acetic acid (LY367385). Male Wistar rats were chronically implanted with recording and stimulating electrodes to enable measurement of evoked potentials from medial perforant path-dentate gyrus granule cell synapses. An injection cannula was inserted into the ipsilateral cerebral ventricle to enable drug application. Experiments were begun 10 days after the implantation procedure. We induced a robust LTP which lasted over 25 h with a 200-Hz tetanization. Injections of LY367385 at all concentrations under investigation (4-32 nmol in a 5-muL injection volume) did not affect basal synaptic transmission. In contrast, we observed a dose-dependent impairment of LTP expression: LY367385 (4 nmol) had no effect on LTP induction, whereas 8 and 16 nmol LY367385 reduced both LTP induction and expression, suggestive of an interaction with N-methyl-D-aspartate receptors. We assessed the effects of daily LY367385 application (8 nmol) on performance in an eight-arm radial maze. LY367385-treated rats showed deficits in reference but not working memory performance compared with vehicle-treated controls. Rearing, grooming and locomotor activity were unaffected by LY367385. These data suggest an important role for mGluR1 in LTP and learning and highlight the specific significance of this mGluR subtype for reference memory.