孤啡肽在嗅周皮层对物体识别记忆的调节作用及其机制研究

Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) system plays an important role in the regulation of learning and memory. Previous studies about the effects of this system on memory mainly focused on spatial and fear memories associated with amygdala and hippocampus. Recently, it was found that perirhinal cortex played a critical role in object recognition memory, NOP receptor also highly expressed in this brain area, however, whether N/OFQ could regulate recognition memory was still unclear. Our previous data indicated that N/OFQ impaired novel object recognition memory after delivered into the lateral ventricular or perirhinal cortex. Thus, we will further investigate the role of N/OFQ in regulating object recognition memory and the underlying mechanisms. In mice novel object recognition, object location recognition and object-in-place recognition models, we will study the effects of N/OFQ infused into the lateral ventricular or perirhinal cortex on the acquisition, consolidation and retrieval of object recognition memories. Then, we will study whether the regulatory effect of N/OFQ on memory is correlated with NMDA or cholinergic receptors. Finally, the effects of N/OFQ on ERK signaling and the expression of c-fos in the perirhinal cortex will be determined. Our research will indicate the role of N/OFQ system in object recognition memories, the acting site and the underlying molecular mechanisms, which will provide novel potential target and theoretic evidences for memory regulation. Our previous data on learning and memory were published in Neuropharmacology, Neurobiology of Learning and Memory, etc.

孤啡肽及其受体在学习记忆调节中起重要作用，目前研究主要集中于海马和杏仁核相关的空间及恐惧记忆。研究表明嗅周皮层在物体识别记忆中起关键作用，孤啡肽受体亦高表达于嗅周皮层，而孤啡肽对此记忆的调节作用尚不清楚。前期实验发现孤啡肽在中枢及嗅周皮层均显著损伤新物体识别记忆，故本项目将进一步研究孤啡肽对物体识别记忆的作用及其机制。在小鼠新物体识别、物体顺序识别及物体位置识别模型中，研究孤啡肽在中枢和嗅周皮层对记忆获取、巩固及回想阶段的作用，检测孤啡肽在记忆调节中与NMDA受体或胆碱能受体的关系，研究孤啡肽在记忆调节中对嗅周皮层ERK信号及c-fos表达的影响。本项目旨在阐明孤啡肽对物体识别记忆的调节作用、作用位点及分子机制，为该记忆的调节提供理论依据和新的药物靶点。申请人在学习记忆方面的研究工作发表于Neuropharmacology，Neurobiol Learn and Mem等期刊。

孤啡肽及其受体在学习记忆调节中起重要作用，目前研究主要集中于海马和杏仁核相关的空间及恐惧记忆。研究表明嗅周皮层在物体识别记忆中起关键作用，孤啡肽受体亦高表达于嗅周皮层，而孤啡肽对此记忆的调节作用尚不清楚。本项目首次揭示了孤啡肽在嗅周皮层对新物体识别记忆的作用及其机制。在小鼠新物体识别模型中，孤啡肽在中枢选择性损伤新物体识别记忆的获取，而对巩固和回想阶段没有明显影响。然后，我们发现嗅周皮层注射孤啡肽也能削弱物体时别记忆，并且还能降低嗅周皮层c-fos的表达，说明嗅周皮层在孤啡肽损伤记忆中发挥了关键作用。此外，结果表明孤啡肽和MK801能协同损伤记忆，说明孤啡肽可能抑制了MNDA受体的谷氨酸能活性。本项目阐明了孤啡肽对物体识别记忆的调节作用、作用位点及分子机制，为该记忆的调节提供理论依据和新的药物靶点。