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内源性大麻素限制代谢型谷氨酸5受体介导的纹状体投射神经元的突触抑制。

Endocannabinoids limit metabotropic glutamate 5 receptor-mediated synaptic inhibition of striatal principal neurons.

作者信息

Centonze Diego, Rossi Silvia, Prosperetti Chiara, Gasperi Valeria, De Chiara Valentina, Bari Monica, Tscherter Anne, Febbraro Fabia, Bernardi Giorgio, Maccarrone Mauro

机构信息

Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.

出版信息

Mol Cell Neurosci. 2007 Jun;35(2):302-10. doi: 10.1016/j.mcn.2007.03.005. Epub 2007 Mar 15.

DOI:10.1016/j.mcn.2007.03.005
PMID:17434747
Abstract

Synaptic transmission in the striatum is regulated by metabotropic glutamate (mGlu) receptors through pre- and postsynaptic mechanisms. We investigated the involvement of mGlu 1 and 5 receptors in the control of both excitatory and inhibitory transmission in the striatum. The mGlu 1 and 5 receptor agonist 3,5-DHPG failed to affect glutamate transmission, while it caused a biphasic effect on GABA transmission, characterized by early increase and late decrease in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from striatal principal neurons. Both mGlu 1 and 5 receptors were involved in the early response to 3,5-DHPG, through membrane depolarization of striatal GABAergic interneurons and action potential generation. The 3,5-DHPG-mediated late depression of inhibitory inputs to striatal principal neurons was conversely secondary to mGlu 5 receptor activation and subsequent endocannabinoid release. In conclusion, we have identified an mGlu-dependent mechanism of GABA transmission regulation of potential relevance for physiological neuronal activity.

摘要

纹状体中的突触传递受代谢型谷氨酸(mGlu)受体通过突触前和突触后机制调控。我们研究了mGlu 1和5受体在纹状体兴奋性和抑制性传递控制中的作用。mGlu 1和5受体激动剂3,5 - 二羟基苯甘氨酸(3,5-DHPG)未能影响谷氨酸传递,而它对GABA传递产生双相效应,其特征是从纹状体主要神经元记录到的自发性抑制性突触后电流(sIPSCs)频率先增加后降低。mGlu 1和5受体都通过纹状体GABA能中间神经元的膜去极化和动作电位产生参与了对3,5-DHPG的早期反应。相反,3,5-DHPG介导的对纹状体主要神经元抑制性输入的晚期抑制继发于mGlu 5受体激活及随后的内源性大麻素释放。总之,我们确定了一种mGlu依赖性的GABA传递调节机制,这可能与生理神经元活动相关。

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