Endocannabinoid-mediated long-term depression in the avian inferior colliculus

描述(申请人提供)：这个项目的主要目标是确定听觉中脑中长期突触可塑性的机制。具体地说，我们打算阐明来自视顶盖(OT，相当于哺乳动物的上丘)的反馈在调节下丘突触强度中的作用。在鸟类和哺乳动物中，这种视觉反馈都与依赖经验的学习有关。我们获得了鸡下丘(EX)外核神经元突触输入的突触特异性长期抑制(LTD)的证据。这种LTD由传入通路的高频刺激触发，需要代谢性谷氨酸受体(MGluR)、突触前N-甲基-D-天冬氨酸受体(NMDAR)和大麻素1受体(CB1R)的激活(Penzo和Pena，2008)。我们收集的初步数据表明，OT促进了较低频率的LTD诱导，可能是通过直接激活mGluRs。此外，我们假设mGluR激活导致谷氨酸逆行释放并激活突触前NMDAR。在这里，我们将解决两个主要问题：谷氨酸受体在听觉中脑突触可塑性中的作用以及OT对下丘突触强度的调节。根据初步结果，所提出的方法已被证明是一种将突触可塑性纳入学习和行为背景的可信的方法。因此，从这项研究中收集的知识将使我们进一步了解学习和记忆的基础。

DESCRIPTION (provided by applicant): The main goal of this project is to identify mechanisms of long-term synaptic plasticity in the auditory midbrain. Specifically, we intend to elucidate the role of feedback from the Optic Tectum (OT, equivalent to the mammalian superior colliculus) in modulating synaptic strength in the inferior colliculus. This visual feedback has been implicated in experience-dependent learning in both birds and mammals. We have obtained evidence of a synapse-specific long-term depression (LTD) of synaptic inputs onto neurons of the external nucleus of the inferior colliculus (EX) in chicken. This LTD is triggered by high-frequency stimulation of the afferent pathway and requires metabotropic glutamate receptor (mGluR), presynaptic N- methyl-D-aspartate receptor (NMDAR) and cannabinoid 1 receptor (CB1R) activation (Penzo and Pena 2008). We have collected preliminary data indicating that OT facilitates LTD induction at lower frequencies, possibly through the direct activation of mGluRs. Furthermore, we hypothesize that mGluR activation leads to retrograde glutamate release and activates presynaptic NMDARs. Here, we will address two main questions: the role of glutamate receptors in synaptic plasticity in the auditory midbrain as well as OT modulation of synaptic strength in the inferior colliculus. In light of the preliminary results the propose methodology have proven to be a plausible way of taking synaptic plasticity into the context of learning and behavior. Therefore, the knowledge gathered from this study will take us a step further to understanding the bases of learning and memory.