ELEVATED LEVELS OF GLUTAMATE AT CEREBELLAR SYNAPSES

提出了一系列实验来确定在中枢兴奋性突触检测到的谷氨酸浓度升高的机制和后果。这个问题的根源是，在形态上定义的突触连接处，每个入侵动作电位是否可以释放一个以上的囊泡(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信条，即在刺激后，每个部位只释放一个水泡(一个部位，一个水泡假说)。基于小脑浦肯野神经元的一系列膜贴片实验，我们将构建一个受体动力学模型。这个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性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.