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.
Sheng Li Xue Bao. 2009 Dec 25;61(6):511-6.
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 x 40 cm x 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 low-frequency 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.
为研究长时程抑制（LTD）在大鼠海马体学习和记忆机制中的作用，对自由活动的动物进行记录。这些动物已在海马体CA1区慢性植入记录电极，并在同侧的Schaffer侧支-连合通路植入双极刺激电极。记录电极插入前囟后3.8毫米、中线右侧2.8毫米处，刺激电极通过颅骨钻孔插入前囟后4.8毫米、中线右侧3.8毫米处。整个组件通过动物头部的橡胶插座连接，然后用牙科水泥固定。通过电生理标准和死后组织学分析确认电极正确放置在海马体CA1区域。手术恢复2周后，将大鼠置于熟悉的记录室3天。用持续时间为0.2毫秒的方波恒流脉冲，以0.033赫兹的频率和调整刺激强度以使场兴奋性突触后电位（fEPSP）幅度达到最大值的50%进行刺激，诱发fEPSP，并在每天同一时间在熟悉的记录环境中记录fEPSP基线3天。准备一个由透明有机玻璃制成的新奇环境（40厘米×40厘米×40厘米），我们研究暴露于新奇空间环境是否促进大鼠海马体CA1突触处活动依赖性突触传递持续减少（即LTD）的表达。结果表明，在没有其他外源性高频或低频刺激方案的情况下，短暂暴露于新奇环境10分钟可促进海马体CA1区LTD的表达。这种促进作用依赖于D1/D5受体的激活：D1/D5受体拮抗剂SCH23390可防止新奇探索期间海马体突触传递的减少。这些数据提供了重要证据，表明LTD可能是某些形式学习和记忆的基础，并且多巴胺参与海马体空间信息存储过程中的突触可塑性。
