Wirkungsweise von Capsaicin auf die synaptische Plastizität in der lateralen Amygdala

辣椒素对外侧杏仁核突触可塑性的影响

• 批准号: 133119739
• 负责人: Privatdozentin Dr. Doris Albrecht
• 金额: --
• 依托单位: Institut für Neurophysiologie (CCM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/133119739?language=en
• 关键词: Wirkungsweise; von; Capsaicin; auf; die

The amygdala plays critical roles in certain types of emotional memory. The underlying mechanisms are believed to depend on activity-dependent long-term potentiation (LTP) and depression (LTD) in the lateral nucleus of the amygdala (LA). In preliminary experiments we have shown that in the LA transient receptor potential proteins from subtype vannilloid 1 (TRPV1) are expressed both in glial and neuronal membranes. TRPV1 receptors have classically been defined as heat-sensitive, ligand gated (among others: capsaicin), nonselective cation channels that integrate nociceptive stimuli in sensory neurons. Here we report that TRPV1 channel activation by capsaicin dose-dependently reduced or suppressed high-frequency-induced LA-LTP. In contrast, from the literature it is known that capsaicin enhances LTP in the CA1 region of the hippocampus, whereas TRPV1 gene-deficient mice show a reduced CA1-LTP. Whereas low-frequency stimulation of cortical fibers did not induce reliable LA-LTD, capsaicin was necessary and sufficient to trigger low frequency-induced LA-LTD. The aim of the project is to clarify which mechanisms are involved in the action of capsaicin on amygdaloid plasticity changes. The results will show which involvement may have pre- and/or postsynaptic mechanisms and detect possible signal cascades. The demonstration of possible TRPV1-mediated plasticity changes after stress (social isolation, forced swim test) should document a relevance of the TRPV1 in long-term changes in physiological and pathological circuit behavior during learning.

杏仁核在某些类型的情绪记忆中起着关键作用。杏仁核外侧核的活动依赖性长时程增强（LTP）和抑制（LTD）是其主要机制。在初步的实验中，我们已经表明，在LA的瞬时受体电位蛋白从亚型vannilloid 1（TRPV 1）表达在神经胶质细胞和神经元膜。TRPV 1受体已被经典地定义为热敏感的、配体门控的（其中包括：辣椒素）、非选择性阳离子通道，其在感觉神经元中整合伤害性刺激。在这里，我们报告，TRPV 1通道激活辣椒素剂量依赖性地减少或抑制高频诱导的LA-LTP。相反，从文献中已知辣椒素增强海马CA 1区的LTP，而TRPV 1基因缺陷小鼠显示CA 1-LTP降低。而低频刺激皮层纤维没有引起可靠的LA-LTD，辣椒素是必要的，足以触发低频诱导的LA-LTD。该项目的目的是澄清哪些机制参与辣椒素杏仁核可塑性变化的行动。结果将显示哪些参与可能具有突触前和/或突触后机制，并检测可能的信号级联。应激后TRPV 1可能介导的可塑性变化（社会隔离，强迫游泳试验）的演示应记录TRPV 1在学习过程中生理和病理回路行为的长期变化中的相关性。