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

描述（由申请人提供）：该项目的主要目标是确定听觉中脑长期突触可塑性的机制。具体来说，我们打算阐明反馈的作用，从视顶盖（OT，相当于哺乳动物上级丘）在调节突触强度下丘。这种视觉反馈与鸟类和哺乳动物的经验依赖性学习有关。我们获得了鸡下丘外核神经元突触特异性长时程抑制的证据。该LTD由传入通路的高频刺激触发，需要代谢型谷氨酸受体（mGluR）、突触前N-甲基-D-天冬氨酸受体（NMDAR）和大麻素1受体（CB 1 R）激活（Penzo和佩纳2008）。我们已经收集了初步的数据表明，OT促进LTD诱导在较低的频率，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的突触可塑性中的作用，以及在下丘的突触强度的OT调制。根据初步的结果，提出的方法已被证明是一个合理的方式，把突触可塑性的背景下学习和行为。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.