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多巴胺D1/D5受体对前额叶皮层V层神经元兴奋性突触输入的调节

Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons.

作者信息

Seamans J K, Durstewitz D, Christie B R, Stevens C F, Sejnowski T J

机构信息

Howard Hughes Medical Institute and Molecular and Computational Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):301-6. doi: 10.1073/pnas.98.1.301.

Abstract

Dopamine acts mainly through the D1/D5 receptor in the prefrontal cortex (PFC) to modulate neural activity and behaviors associated with working memory. To understand the mechanism of this effect, we examined the modulation of excitatory synaptic inputs onto layer V PFC pyramidal neurons by D1/D5 receptor stimulation. D1/D5 agonists increased the size of N-methyl-d-aspartate (NMDA) component of excitatory postsynaptic currents (EPSCs) through a postsynaptic mechanism. In contrast, D1/D5 agonists caused a slight reduction in the size of the non-NMDA component of EPSCs through a small decrease in release probability. With 20 Hz synaptic trains, we found that the D1/D5 agonists increased depolarization of summating the NMDA component of excitatory postsynaptic potential (EPSP). By increasing the NMDA component of EPSCs, yet slightly reducing release, D1/D5 receptor activation selectively enhanced sustained synaptic inputs and equalized the sizes of EPSPs in a 20-Hz train.

摘要

多巴胺主要通过前额叶皮质(PFC)中的D1/D5受体发挥作用,以调节与工作记忆相关的神经活动和行为。为了解这种作用机制,我们研究了D1/D5受体刺激对V层PFC锥体神经元兴奋性突触输入的调节。D1/D5激动剂通过突触后机制增加了兴奋性突触后电流(EPSCs)中N-甲基-D-天冬氨酸(NMDA)成分的大小。相比之下,D1/D5激动剂通过释放概率的小幅降低,使EPSCs的非NMDA成分大小略有减少。在20 Hz突触串刺激下,我们发现D1/D5激动剂增加了兴奋性突触后电位(EPSP)中NMDA成分总和的去极化。通过增加EPSCs的NMDA成分,但略微减少释放,D1/D5受体激活选择性地增强了持续的突触输入,并使20 Hz串刺激中EPSP的大小趋于均衡。

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