ELEVATED LEVELS OF GLUTAMATE AT CEREBELLAR SYNAPSES

我们提出了一系列的实验来确定谷氨酸在中枢兴奋性突触检测到的升高的机制和后果。这个问题的根源在于每个入侵动作电位在形态学上确定的突触连接处是否可以释放多个囊泡（多囊泡释放；MVR）。虽然MVR被认为发生在培养的海马神经元上，但最近提出了另一种机制。MVR挑战了神经科学的一个原则，即每个部位只有一个囊泡在刺激后被释放（一个部位，一个囊泡假说）。基于一系列小脑浦肯野神经元的膜贴片实验，建立受体动力学模型。该模型将与操作相结合，以区分可能导致谷氨酸浓度升高的机制。了解神经递质浓度升高的来源和可能的后果将为中枢突触传递提供有价值的见解。

A series of experiments are proposed to determine the mechanism and consequence of elevated glutamate concentration detected at central excitatory synapses. At the source of this question is the whether more than one vesicle can be released at a morphologically defined synaptic junction per invading action potential (multivesicular release; MVR). While MVR has been suggested to occur on cultured hippocampal neurons, an alternative mechanism has recently been proposed. MVR challenges a tenet of neuroscience that states that only one vesicle at each site is released following a stimulus (one-site, one vesicle hypothesis). A model of receptor kinetics will be constructed based on a series of membrane patch experiments from Purkinje neurons of the cerebellum. This model will be combined with manipulations to distinguish the mechanisms that may be responsible for elevated glutamate concentrations. Understanding the source of elevated neurotransmitter concentration and possible consequences will provide valuable insight to central synaptic transmission.