OPIOID RECEPTORS IN INDUCTION OF LONG TERM POTENTIATION

阿片受体诱导长期增强

• 批准号: 6395904
• 负责人: JOSEPH A REYES
• 金额: $ 12.7万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6395904
• 关键词: data collection methodology /evaluation; dentate nucleus; electrophysiology; gene expression; in situ hybridization; laboratory rat; long term potentiation; neural plasticity; neurophysiology; opioid receptor; protooncogene; receptor expression; regulatory gene

Long-Term Potentiation (LTP), is an enhancement of evoked neurotransmission which appears within minutes after brief, tetanic stimulation of an afferent, monosynaptic neural pathway and lasts from hours to weeks. LTP has been widely studied as a model of cellular information storage, and there is growing evidence implicating LTP-like mechanisms in memory processes. Three processes appear to be necessary for development of LTP: 1) postsynaptic depolarization, 2) activation of the voltage dependent glutamate receptor N-methyl-D-aspartate (NMDA), and 3) the influx of Ca++ into the postsynaptic terminal. However, some of the classic glutamatergic pathways in the rat hippocampal formation have been reported to contain opioid peptides. It has recently been demonstrated that opioid peptide release and/or opioid peptide receptor activation is necessary for LTP formation in these pathways. Taken together, opioid peptide regulation may be necessary for mechanisms associated with synaptic plasticity and learning. In the studies proposed, the dependence of lateral and medial perforant path-dentate gyrus LTP on opioid peptide receptors will be investigated using intra-hippocampal administration of either CTOP (mu-receptor specific antagonist), NTI (delta-receptor specific antagonist), nor-BNI (kappa-receptor specific antagonist) or the NMDA antagonists CPP. In addition, it is important to understand the relationship between opioid receptor activation and intracellular molecular events needed to induced potentiation. Understanding the cellular basis of LTP induction may elucidate molecular mechanism underlying long-term changes associated with memory formation. The expression of protooncogenes or immediate-early genes (IEG) can be induced in phasic electrophysiological events. The protein products of these IEG's work as nuclear transcription factors selectively regulating target genes associated with long-term alterations in cellular development and plasticity. Interestingly, high frequency stimulation of the mossy fibers in the hippocampus induces IEG activity in the dentate, and this expression is blocked by naloxone, which also blocks LTP induction. These data suggest IEG transcription and translocation may be a mechanism underlying opioid receptor dependent LTP maintenance. Specific Aim 2 will examine whether expression of the IEG's c-fos, fra-1 and fos-b are associated with induction of LTP in either the literal and/or the medial perforant path-dentate gyrus LTP.

长时程增强(LTP)，是诱发的增强 短暂的破伤风后几分钟内出现的神经传递 刺激传入、单突触的神经通路，并从 几个小时到几个星期。LTP作为一种细胞模型已被广泛研究 信息存储，越来越多的证据表明与LTP有关 记忆过程中的机制。似乎有三个过程是必要的 LTP的发展：1)突触后去极化，2)激活 电压依赖性谷氨酸受体N-甲基-D-天冬氨酸(NMDA)，和3) 钙离子流入突触后终末。然而，一些 大鼠海马结构中经典的谷氨酸能通路已经被 据报道含有阿片肽。它最近已经被证明是 阿片肽释放和/或阿片肽受体激活是 在这些途径中LTP的形成是必需的。加在一起，阿片类药物 肽调节可能是与以下相关的机制所必需的 突触可塑性和学习。在建议的研究中，依赖 外侧和内侧穿支路-齿状回LTP对阿片肽的影响 将通过海马区内给药来研究受体 CTOP(Mu受体特异性拮抗剂)、NTI(增量受体 特异性拮抗剂)、Nor-BNI(kappa受体特异性拮抗剂)或 NMDA拮抗剂CPP。此外，了解 阿片受体激活与细胞内的关系 诱导增强所需的分子事件。了解 LTP诱导的细胞学基础可能阐明分子机制 与记忆形成相关的潜在的长期变化。这个 可以诱导原癌基因或即刻早期基因(IEG)的表达 在相位性电生理事件中。这些IEG的蛋白质产品 作为核转录因子选择性地调节靶基因 与细胞发育的长期变化和 可塑性。有趣的是，对苔藓纤维的高频刺激 在海马体中诱导齿状体内的IEG活动，这 表达被纳洛酮阻断，纳洛酮也阻断LTP的诱导。这些 数据表明IEG转录和易位可能是一种机制 潜在的阿片受体依赖的LTP维持。特定目标2将 检查IEG的c-fos、fra-1和fos-b的表达是否 与字面和/或内面的LTP的诱导有关 穿通径-齿状回LTP。