MECHANISMS OF AMPA RECEPTOR-MEDIATED EPSC TIME COURSE

提出了一系列实验，以更高程度地估计 精确度谷氨酸浓度的时间进程和大小 突触裂隙突触小泡吐出后的突触裂隙一个 AMPA受体动力学的数学模型将通过 离体膜贴片用于CA1的一系列动力学实验 海马神经元。该模型将与AMPA的录音相结合 培养的CA1海马神经元受体介导的突触反应 以达到谷氨酸瞬变的大小和形状的估计。 而类似的实验已经对NMDA受体进行了 反应，更快的AMPA受体动力学将导致实质性的 时间分辨率的提高，使我们能够更准确地预测 谷氨酸瞬变的早期阶段，因此， 突触后AMPA受体，在突触反应过程中被激活。 这一预测严重影响了最近提出的 突触可塑性与多囊泡的生理意义 将在另一组实验中进行测试，旨在 确定AMPA受体是否因单个量子事件而饱和 在被唤起的反应中。了解AMPA在何种程度上 受体在突触反应过程中被结合和激活 有关调节效应问题的宝贵见解，请参阅 突触水平，被认为是调节突触的各种机制 功效，包括长期增强作用。

A series of experiments are proposed to estimate with a higher degree of accuracy the time course and magnitude of the glutamate concentration in the synaptic cleft following exocytosis of a synaptic vesicle. A mathematical model of AMPA receptor kinetics will be refined through a series of kinetic experiments using excised membrane patches from CA1 hippocampal neurons. This model will be combined with recordings of AMPA receptor-mediated synaptic responses in cultured CA1 hippocampal neurons to reach an estimate of the size and shape of the glutamate transient. While similar experiments have been performed with NMDA receptor responses, the faster-AMPA receptor kinetics will result in a substantial improvement in temporal resolution, allowing us to predict more accurately the early phase of the glutamate transient and, therefore, the fraction of postsynaptic AMPA receptors that is activated during a synaptic response. This prediction, which impacts heavily on recently proposed mechanisms of synaptic plasticity and the physiological importance of multivesicular release, will be tested in another set of experiments designed to determine whether AMPA receptors are saturated by a single quantal event and during evoked responses. Understanding the degree to which AMPA receptors are bound and activated during a synaptic response will provide valuable insight into questions regarding the modulatory effects, at the synaptic level, of various mechanisms thought to regulate synaptic efficacy, including long-term potentiation.