OPIOID RECEPTORS IN INDUCTION OF LONG TERM POTENTIATION

阿片受体诱导长期增强

• 批准号: 6107762
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107762
• 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）是一种增强诱发电位的方法。 短暂强直后几分钟内出现的神经传递 刺激传入、单突触神经通路并持续 几小时到几周LTP作为一种细胞模型已经被广泛研究， 信息存储，并且有越来越多的证据表明LTP类似 记忆过程中的机制。三个过程似乎是必要的 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） Ca ~（++）内流到突触后末梢。但部分 在大鼠海马结构中的经典多巴胺能通路已经被 含有阿片肽最近有证据表明 阿片肽释放和/或阿片肽受体激活 在这些途径中形成LTP所必需的。综合来看，阿片类药物 肽调节可能是必要的机制， 突触可塑性和学习。在这些研究中， 外侧和内侧穿支-齿状回LTP对阿片肽的影响 将使用海马内施用 CTOP（μ受体特异性拮抗剂）、NTI（δ受体） 特异性拮抗剂）、nor-BNI（κ受体特异性拮抗剂）或 NMDA拮抗剂CPP。此外，重要的是要了解 阿片受体激活与细胞内 诱导增强所需的分子事件。了解 LTP诱导的细胞基础可能阐明分子机制 与记忆形成相关的潜在长期变化。的 可以诱导原癌基因或立即早期基因（IEG）的表达 阶段性电生理事件。这些IEG的蛋白质产物 作为核转录因子选择性地调节靶基因 与细胞发育的长期改变有关， 可塑性有趣的是，高频刺激苔藓纤维 在海马体中诱导齿状回的IEG活动， 表达被纳洛酮阻断，纳洛酮也阻断LTP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性LTP维持。具体目标2将 检测IEG的c-fos、fra-1和fos-b的表达是否 与字面和/或中间的LTP诱导相关 穿通通路-齿状回LTP。