Wirkungsweise von Capsaicin auf die synaptische Plastizität in der lateralen Amygdala

杏仁核在某些类型的情绪记忆中起着关键作用。潜在的机制被认为依赖于活动依赖性的长期增强（LTP）和杏仁核外侧核（LA）的抑制（LTD）。在初步实验中，我们已经发现在LA中瞬时受体电位蛋白亚型vannilloid 1 （TRPV1）在胶质和神经元膜中均有表达。TRPV1受体传统上被定义为热敏的、配体门控的（其中包括辣椒素）、非选择性阳离子通道，它们在感觉神经元中整合伤害性刺激。在这里，我们报告了辣椒素激活TRPV1通道的剂量依赖性降低或抑制高频诱导的LA-LTP。相比之下，从文献中得知，辣椒素增强了海马CA1区域的LTP，而TRPV1基因缺陷小鼠的CA1-LTP则降低。而低频刺激皮质纤维不能诱导可靠的LA-LTD，辣椒素是触发低频诱导的LA-LTD的必要和充分条件。该项目的目的是澄清哪些机制参与辣椒素对杏仁核可塑性变化的作用。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（社会隔离、强迫游泳测试）后TRPV1介导的可塑性变化可能证明了TRPV1与学习过程中生理和病理回路行为长期变化的相关性。

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.