mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.
mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.
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DOI：
10.1371/journal.pone.0070415
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lu HC
中科院分区：
文献类型：
--
作者：
Jew CP;Wu CS;Sun H;Zhu J;Huang JY;Yu D;Justice NJ;Lu HC
I组代谢型谷氨酸受体5（mGluR 5）已经涉及各种神经障碍的病理学，包括精神分裂症、ADHD和自闭症。mGluR 5依赖性突触可塑性已经在多种神经连接中被描述，并且其信号传导已经涉及几种行为。这些行为包括对新环境的运动反应、感觉运动门控、焦虑和认知。mGluR 5在不同脑区的谷氨酸能神经元、抑制性神经元和神经胶质中表达。在这项研究中，我们表明，删除mGluR 5表达只在主皮层神经元导致缺陷的大麻素受体1（CB 1 R）依赖的突触可塑性在前额叶皮层。这些皮质谷氨酸能mGluR 5基因敲除小鼠表现出增加的新奇诱导的运动，并且它们的运动可以通过用精神兴奋剂哌甲酯治疗而进一步增强。尽管重复行为适度减少，但皮层神经元能mGluR 5敲除小鼠在感觉运动门控、焦虑、运动平衡/学习和恐惧条件反射行为方面是正常的。这些结果表明，mGluR 5信号在皮层神经元所需的精确调节运动反应的一个新的环境，但不是感觉运动门控，焦虑，运动协调，几种形式的学习或社会互动。
The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R) dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.
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