Role of hippocampal CA3 μ-opioid receptors in spatial learning and memory
Role of hippocampal CA3 μ-opioid receptors in spatial learning and memory
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DOI：
10.1523/jneurosci.5569-03.2004
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发表时间：
2004-03-24
影响因子：
5.3
通讯作者：
Martinez, JL
中科院分区：
文献类型：
--
作者：
Meilandt, WJ;Barea-Rodriguez, E;Martinez, JL
海马体的背侧CA 3区在其连接性、对神经毒性病变的敏感性以及编码和检索情景记忆的能力方面是独特的。CA 3区域的计算模型预测，阻断CA 3的苔藓纤维和/或穿孔路径活动将分别导致学习和空间记忆回忆的损害。由于CA 3区含有μ-阿片受体，并从苔藓纤维和侧向穿孔通路接收输入，这两者都含有并释放阿片肽，我们测试了CA 3区的μ-阿片受体失活将导致空间学习和记忆障碍和检索缺陷的假设。在这项研究中，雄性Sprague道利大鼠在单次双侧海马内注射生理盐水或选择性和不可逆的μ-阿片受体拮抗剂β-funalcidamine（β-FNA）到CA 3区后，在Morris水迷宫中进行训练。我们发现，μ阿片受体结合减少β-FNA注射后24小时，注射后11天恢复到对照水平。将β-FNA注射到CA 3区，但不注射到脑室，会导致空间学习获得的显著障碍，而不会导致感觉或运动缺陷。一旦μ-阿片受体水平得到补充（注射后>11天），新的学习不会受到影响。在预先训练的动物中，β-FNA显著损害了空间记忆提取和新的（逆转）学习。这些数据与CA 3功能的理论模型一致，并表明CA 3 μ阿片受体在空间记忆的获得和检索中发挥着重要作用。
The dorsal CA3 region of the hippocampus is unique in its connectivity, sensitivity to neurotoxic lesions, and its ability to encode and retrieve episodic memories. Computational models of the CA3 region predict that blocking mossy-fiber and/or perforant path activity to CA3 would cause impairments in learning and recall of spatial memory, respectively. Because the CA3 region contains mu-opioid receptors and receives inputs from the mossy-fiber and lateral perforant pathways, both of which contain and release opioid peptides, we tested the hypothesis that inactivating mu-opioid receptors in the CA3 region would cause spatial learning and memory impairments and retrieval deficits. In this study, male Sprague Dawley rats were trained in a Morris water maze after a single bilateral intrahippocampal injection of either saline or the selective and irreversible mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) into area CA3. We found that mu-opioid receptor binding decreased 24 hr after beta-FNA injection and returned to control levels 11 d after injection. Injections of beta-FNA into the CA3 region, but not into the ventricles, caused a significant impairment in the acquisition of spatial learning without causing sensory or motor deficits. New learning was not affected once mu-opioid receptor levels replenished (>11 d after injection). In pretrained animals, beta-FNA significantly impaired spatial memory retrieval and new ( reversal) learning. These data are consistent with theoretical models of CA3 function and suggest that CA3 mu-opioid receptors play an important role in the acquisition and retrieval of spatial memory.