Homeostatic regulation and trafficking of AMPA receptors at single synapses

在中枢神经系统中，一个神经元接收来自许多神经元的大量突触输入。 周围的细胞，与个别的突触作用独立于彼此。突触可塑性， 它是大脑高级功能包括学习和记忆所必需的， 在生理条件下发生。大量的数据表明，无论是赫布型 突触可塑性包括长时程增强（LTP）和长时程抑制（LTD），以及 非赫布型稳态突触可塑性通过调节突触AMPA表达 受体（AMPAR）丰度，通常通过囊泡介导的受体运输。考虑到 可塑性是高度突触特异性的，研究突触特异性，活动依赖性调节， AMPAR的表达将为我们理解突触生理学和大脑提供重要的见解。 功能此外，稳态可塑性仅在神经元群体水平上进行了研究;如果 以及它如何在单个突触上表达仍然是一个谜。为了解决这些问题，我们建立了 神经元培养的两个实验范例，其中可识别的单个突触的活动水平 是有具体规定的。我们将研究AMPAR丰度的细胞机制， 对单个突触的活动变化作出反应而进行特殊调节。该应用程序旨在了解细胞间的强度的机制， 神经元中的通讯是受调节的。通过研究突触特异性，活动依赖性 AMPAR表达的调控，这项研究将为我们理解 突触生理学和大脑功能。

In the central nervous system, a neuron receives a large number of synaptic inputs from many surrounding cells, with individual synapses acting independently of one another. Synaptic plasticity, which is essential for high brain functions including learning and memory, is a synapse autonomous event under physiological conditions. A large amount of data has shown that both Hebbian-type synaptic plasticity including long-term potentiation (LTP) and long-term depression (LTD), as well as non-Hebbian type homeostatic synaptic plasticity are expressed via regulation of synaptic AMPA receptor (AMPAR) abundance, often by vesicle-mediated receptor trafficking. Given the fact that plasticity is highly synapse specific, investigation of synapse specific, activity-dependent regulation of AMPAR expression will provide crucial insights in our understanding of synapse physiology and brain function. Furthermore, homeostatic plasticity has been studied only at the neuronal population level; if and how it is expressed at single synapses remains elusive. To address these issues, we have set up two experimental paradigms in neuronal culture, in which activity levels of identifiable single synapses are specifically regulated. We will investigate the cellular mechanisms by which AMPAR abundance is specifically regulated in response to activity changes at single synapses. The application aims to understand the mechanisms by which the strength of intercellular communication is regulated in neurons. By investigating synapse specific, activity-dependent regulation of AMPAR expression, this study will provide crucial insights in our understanding of synapse physiology and brain function.