AMPA Receptor Cycling in the Retina

AMPA 受体在视网膜中循环

• 批准号: 7847118
• 负责人: SCOTT NAWY
• 金额: $ 6.87万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847118
• 关键词: AMPA Receptors; Binding; Binding Proteins; Biochemical; Biological Assay; Cells; Data; Development; Exhibits; Glutamate Receptor; Glutamates; Hippocampus (Brain); Light; Link; Measures; Mediating; Membrane; Molecular; Mus; Neurons; Pattern; Physiological; Play; Process; Proteins; Regulation; Research Personnel; Retina; Retinal; Retinal Diseases; Retinal Ganglion Cells; Role; Signal Transduction; Site; Stimulus; Surface; Synapses; Synaptic Membranes; Synaptic Receptors; Synaptic Transmission; Synaptic plasticity; Testing; Therapeutic; Time; ganglion cell; human RIPK1 protein; insight; neurotransmission; neurotransmitter release; novel; postsynaptic; programs; receptor; research study; retinal neuron; synaptic function; trafficking; transmission process

The rapid cycling of AMPA receptors (AMPARs) into and out of the membrane maintains neurotransmission at a number of CMS synapses. The cycling of AMPARs in the hippocampus and cortex is dynamically regulated by changes in levels of basal synaptic transmission and has been proposed to play a role in certain forms of synaptic plasticity. It remains unclear, however, whether the cycling of AMPARs also occurs at synapses not believed to exhibit postsynaptic forms of activity dependent plasticity. Additionally the question remains as to whether there are differences in the regulation of receptor trafficking at synapses that are subject to very different patterns of synaptic activation. For example, while many CMS synapses function primarily through intermittent, activity driven neurotransmitter release, synapses in the retina are subject to tonic glutamate release and stimulus dependent cessation of synaptic transmission. We are investigating the trafficking of AMPARs in retinal neurons and its regulation by activity. Our preliminary data demonstrates that, GluR2-c6ntaining AMPARs, can be rapidly cycled at the extrasynaptic membrane in the retina. ; ¿ Wpwever, contrary to in hippocampal synapses, activity in the retina stabilizes AMPARs in a non-cycling*¿""' mpde. This reversible process is modulated by physiological light stimuli. Experiments in this proposal,will jseek to test the hypothesis, that normal light/dark cycles drive changes in the cycling of GluR2 -containihg AMPARs thereby impacting functional signaling in the retina. Experiments in'Aim.l .will establish the physiological conditions that mediate changes in the cycling of AMPARs in the retina. In.Aim 2 we will seek to.determine the molecular mechanisms by which activity links to changes in.the cycling of AMPARs. Finally, inAim 3 we will characterize the physiological significance of altered AMPAR cycling on the function of .. synaptic transmission in the retina. Results from these experiments will greatly enhance our understanding of.the function and regulation.of signaling in the retina potentially identifying the existence a previously . ¿, unknown form activity dependent of retinal plasticity. This should provide valuable insight into possible therapeutic treatments relevant to diseases of retinal development and degeneration. : :

AMPA接收器（AMPARS）迅速循环进入膜，维持神经传递 在许多CMS突触中。海马和皮层中AMPAR的循环是动态的 受基本突触传播水平变化的调节，并已提议在 某些形式的突触可塑性。但是，尚不清楚AMPAR的循环是否也发生 在突触中不认为存在突触后的活性依赖性可塑性。另外 问题仍然是关于突触的受体贩运调节是否存在差异 受到突触激活的非常不同的模式。例如，许多CMS突触功能 首先，通过间歇性，活动驱动的神经递质释放，视网膜中的突触受到 突触传播的补品谷氨酸释放和刺激依赖性停止。我们正在调查 AMPAR在残留神经元中的运输及其通过活动调节。我们的初步数据证明了 这就是Glur2-C6nate Ampars，可以迅速循环在视网膜中的外鼻膜上。 ; WPWEVER，与海马突触形成对比，视网膜的活性稳定了非循环*»“”'''' mpde。这种可逆过程是通过物理光刺激调节的。在此提案中的实验，将 jseek测试假设，正常的光/黑色循环驱动Glur2 -containihg循环的变化 AMPAR从而影响视网膜中的功能信号。 'aim.l。将建立 介导视网膜中AMPAR循环变化的生理条件。 IN.AIM 2我们将寻求 确定活性与AMPAR循环的变化相关的分子机制。最后， INAIM 3我们将表征改变AMPAR循环对..的功能的物理意义。 视网膜中的突触传播。这些实验的结果将大大增强我们的理解 视网膜中的功能和调节。 ，，，， 剩余可塑性的未知形式活性。这应该为可能的宝贵见解 与残余发育和变性疾病有关的治疗治疗。 ：