MOP Receptor Effects on the Hippocampal CA1 Network

MOP 受体对海马 CA1 网络的影响

• 批准号: 6921505
• 负责人: ADAM RORY MCQUISTON
• 金额: $ 22.5万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6921505
• 关键词: bioimaging /biomedical imaging; brain imaging /visualization /scanning; dendrites; drug withdrawal; electrophysiology; hippocampus; innervation; interneurons; laboratory rat; neural transmission; opioid receptor; pyramidal cells; receptor expression; relapse /recurrence; synapses

DESCRIPTION (provided by applicant): The high rate of relapse in opioid drug users is often triggered by the exposure to environmental cues associated with previous drug use. These associations are thought to involve the activation of mu-opioid peptide (MOP) receptors within the hippocampus. MOP receptor activation on GABAergic inhibitory interneurons within the hippocampus inhibits the release of GABA onto pyramidal cells, which can profoundly affect hippocampal network function and modulate the flow of information to other areas of the CNS. It is this change in hippocampal network function that may be involved in the formation of the associations made between environmental cues and chronic drug abuse. Although it is known that MOP receptor activation inhibits GABAergic synaptic transmission, the precise interneurons inhibited by MOP receptor activation and their specific effect on hippocampal CA1 network function is not completely understood. Based on preliminary studies, we hypothesize that MOP receptors inhibit the release of GABA from interneurons that innervate the entire somatic and dendritic extent of CA1 pyramidal cells. Furthermore, we suggest that MOP receptor activation augments excitatory inputs, facilitates the propagation of excitatory information between pyramidal cell compartments, and facilitates the temporal and spatial integration of excitatory activity within the CA1 network. The effects of MOP receptors on hippocampal CA1 network function will be examined using voltage-sensitive dye (VSD) imaging from rat brain slices. VSD imaging will allow us to simultaneously measure both excitatory and inhibitory activity throughout the entire neural network of hippocampal CA1 brain slices with high spatial and temporal resolution. These studies will provide a foundation to address the long-term goals of how chronic opioid use alters MOP receptor and neural network function. The results from these studies will provide important information regarding MOP receptor-induced changes in network activity and may possibly lead to the development of treatments for opioid addiction.

描述（由申请人提供）：阿片类药物使用者的高复发率通常是由暴露于与先前药物使用相关的环境线索引发的。这些关联被认为涉及海马体内mu-阿片肽（MOP）受体的激活。海马GABA能抑制性中间神经元上的MOP受体激活可抑制GABA向锥体细胞的释放，从而深刻影响海马网络功能并调节信息向中枢神经系统其他区域的流动。海马体网络功能的这种变化可能与环境线索和慢性药物滥用之间的关联形成有关。虽然已知MOP受体激活可抑制gaba能突触传递，但被MOP受体激活抑制的中间神经元的具体机制及其对海马CA1网络功能的具体影响尚不完全清楚。基于初步研究，我们假设MOP受体抑制支配CA1锥体细胞整个体细胞和树突范围的中间神经元释放GABA。此外，我们认为MOP受体的激活增加了兴奋性输入，促进了锥体细胞间兴奋性信息的传播，并促进了CA1网络内兴奋性活动的时空整合。MOP受体对海马CA1网络功能的影响将通过大鼠脑切片的电压敏感染料（VSD）成像进行检测。VSD成像将使我们能够以高空间和时间分辨率同时测量海马CA1脑切片整个神经网络的兴奋性和抑制性活动。这些研究将为解决慢性阿片类药物使用如何改变MOP受体和神经网络功能的长期目标提供基础。这些研究结果将为MOP受体诱导的网络活动变化提供重要信息，并可能导致阿片类药物成瘾治疗的发展。