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首页> 外文期刊>The European Journal of Neuroscience >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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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

机译：代谢型谷氨酸受体1的药理拮抗作用通过N-甲基-D-天冬氨酸和代谢型谷氨酸受体依赖性机制调节自由移动大鼠齿状回中的长期增强和空间参考记忆。

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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-microL 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.
机译：I型代谢型谷氨酸受体（mGluRs）对于体内多种形式的海马突触可塑性至关重要。受体亚型mGluR1在长期增强（LTP）和学习中的作用尚不清楚。我们检查了mGluR1对海马LTP的贡献和使用选择性拮抗剂（S）-（+）-α-氨基-4羧基-2-甲基苯乙酸（LY367385）的空间学习。将雄性Wistar大鼠长期植入记录和刺激电极，以测量来自内侧穿孔路径齿状回颗粒细胞突触的诱发电位。将注射套管插入同侧脑室以进行药物应用。植入程序后10天开始实验。我们诱导了一个健壮的LTP，持续200赫兹，持续了25小时。所研究的所有浓度的LY367385注射液（5-microL注射量的4-32 nmol）均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害：LY367385（4 nmol）对LTP诱导没有影响，而8和16 nmol LY367385降低LTP诱导和表达，暗示与N-甲基-d-的相互作用天冬氨酸受体。我们评估了每天施用LY367385（8 nmol）对八臂放射状迷宫性能的影响。与媒介物处理的对照组相比，LY367385处理的大鼠显示出参考缺陷，但没有工作记忆表现。 LY367385不影响饲养，修饰和运动能力。这些数据表明了mGluR1在LTP和学习中的重要作用，并突出了该mGluR亚型对于参考记忆的特殊意义。

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