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多巴胺参与的海马神经元长时程抑制在大鼠新环境探索中的作用

刘娜, 薛彬, 邢华, 徐林, 江善祥

南京农业大学动物医学院兽医药理与毒理学实验室，南京 210095； 中国科学院云南省动物模型与人类疾病机理重点实验室学习记忆学科组，昆明 650223；中南大学湘雅附属第二医院精神卫生研究所，长沙410011； 扬州大学兽医学院，扬州 225009

摘要

本文利用清醒自由移动大鼠研究海马神经元长时程抑制(long-term depression, LTD)在新环境探索中的作用，为进一步研究LTD 在学习记忆机制中的作用提供证据。在大鼠海马CA1 区埋植电极，刺激Schaffer 侧枝记录CA1 区树突层的兴奋性突触后场电位(field excitatory postsynaptic potential, fEPSP)。观察动物探索新环境时海马的fEPSP 变化，了解海马在空间探索学习过程中的信息存储过程；并对多巴胺在海马的空间学习记忆中的作用进行验证。结果显示，动物经过空间探索学习后，海马的fEPSP 出现LTD，这种LTD 依赖于海马多巴胺神经元的活动。以上结果提示，新环境探索产生的内源性LTD 可能是海马空间学习记忆潜在的细胞水平机制，多巴胺在此过程中起到重要的调节作用。

关键词： 长时程抑制; 多巴胺; 海马; 新环境探索行为; 大鼠

分类号：Q424

[Dopamine-dependent long-term depression in hippocampus of rat induced by exposure to spatial novelty.] [Ariticle in Chinese]

LIU Na, XUE Bin, XING Hua, XU Lin, JIANG Shan-Xiang

Laboratory of Veterinary Pharmacology and Toxicology, Animal Medicine College, Nanjing Agriculture University, Nanjing 210095, China； Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences &； Yunnan Province, Laboratory of Learning and Memory, Kunming Institute of Zoology, Kunming 650223, China； Mental Health Institute of the 2nd Xiangya Hospital, Central South University, Changsha 410011, China； 4Veterinary Medicine College, Yangzhou University, Yangzhou 225009, China

Abstract

To study the role of long-term depression (LTD) in the mechanisms of learning and memory in hippocampus of rat, recordings were taken from freely moving animals that had undergone chronic implantation of a recording electrode in the hippocampus CA1 region and a bipolar stimulating electrode in the ipsilateral Schaffer collateral–commissural pathway. The recording electrode was inserted 3.8 mm posterior to bregma and 2.8 mm right of the midline, and the stimulating electrode was inserted 4.8 mm posterior to bregma and 3.8 mm right of the midline via holes drilled through the skull. The entire assembly was connected with a rubber socket on the animal’s head and then stabilized with dental cement. The correct placement of the electrodes into the hippocampal CA1 area was confirmed via electrophysiological criteria and postmortem histological analysis. After 2 weeks of surgery recovery, the rats were placed in the familiar recording chamber for 3 days. The field excitatory postsynaptic potentials (fEPSPs) were evoked by stimulating with a square wave constant current pulse of 0.2 ms duration, at a frequency of 0.033 Hz and at a stimulation intensity adjusted to given an fEPSP amplitude of 50% of the maximum, and the baseline of fEPSPs were recorded for 3 days in the familiar recording environment at the same time each day. A novelty environment that was made of clear Perspex (40 cm× 40 cm× 40 cm) was prepared and we examined whether exposure to a novelty spatial environment facilitated the expression of activity-dependent persistent decrease in synaptic transmission (namely LTD) at CA1 synapses in the rat hippocampus. The results showed that brief exposure to a novelty environment for 10 min facilitated the expression of LTD in the hippocampal CA1 area under no other exogenous high- or lowfrequency stimulation protocol. This facilitatory effect was dependent on the activation of D1/D5 receptors: the D1/D5 receptors antagonist SCH23390 prevented the decrease of synaptic transmission in the hippocampus during the novelty exploration. These data provided important evidence that LTD may underlie certain forms of learning and memory and that dopamine participates in the synaptic plasticity in the process of hippocampal spatial information storage.

Key words: long-term synaptic depression; dopamine; hippocampus; exploratory behavior; rats

收稿日期：2009-07-27　　录用日期：2009-11-03

通讯作者：徐林,江善祥　　E-mail: nauvy@sina.com,

引用本文：

刘娜, 薛彬, 邢华, 徐林, 江善祥. 多巴胺参与的海马神经元长时程抑制在大鼠新环境探索中的作用[J]. 生理学报 2009; 61 (6): 511-516.

LIU Na, XUE Bin, XING Hua, XU Lin, JIANG Shan-Xiang. [Dopamine-dependent long-term depression in hippocampus of rat induced by exposure to spatial novelty.] [Ariticle in Chinese] . Acta Physiol Sin 2009; 61 (6): 511-516 (in Chinese with English abstract).