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

内源性大麻素介导的禽类下丘长期抑制

• 批准号: 7676921
• 负责人: Mario A Penzo
• 金额: $ 4.12万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-23 至 2011-02-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7676921
• 关键词: Address; Afferent Pathways; Agonist; Auditory; Axon; Behavior; Birds; Calcium; Cannabinoids; Cell Nucleus; Cells; Chickens; Cues; Data; Dendrites; Endocannabinoids; Feedback; Frequencies; Glutamate Receptor; Glutamates; Goals; Inferior Colliculus; Knowledge; Lead; Learning; Life; Light; Location; Long-Term Depression; Mammals; Mediating; Memory; Metabotropic Glutamate Receptors; Methodology; Midbrain structure; N-Methyl-D-Aspartate Receptors; Neurons; Play; Process; Receptor Activation; Reporting; Role; Signal Transduction; Synapses; Synaptic plasticity; Vertebral column; base; cannabinoid receptor; experience; postsynaptic; presynaptic; response; superior colliculus Corpora quadrigemina; visual feedback; visual information

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.

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，我们打算阐明视顶盖（OT，相当于哺乳动物上丘）的反馈在调节下丘突触强度中的作用。这种视觉反馈与鸟类和哺乳动物的经验依赖学习有关。我们已经获得了鸡下丘外核（EX）神经元突触输入的突触特异性长期抑制（LTD）的证据。这种LTD是由传入通路的高频刺激触发的，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（CB1R）激活（Penzo和Pena 2008）。我们收集的初步数据表明，OT 可能通过直接激活 mGluR，促进较低频率下的 LTD 诱导。此外，我们假设 mGluR 激活导致逆行谷氨酸释放并激活突触前 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下丘突触强度的 OT 调节。根据初步结果，所提出的方法已被证明是将突触可塑性纳入学习和行为背景的一种可行方法。因此，从这项研究中收集的知识将让我们进一步了解学习和记忆的基础。