Regulation of calcium-secretion coupling

钙分泌偶联的调节

• 批准号: 171404-2011
• 负责人: Sossin, Wayne
• 金额: $ 3.5万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629393
• 关键词: Regulation; calcium; secretion; coupling

Neurons communicate with each other at synapses. When the action potential reaches the presynaptic side of the synapse, the electrical signal is turned into a chemical signal through the calcium-dependent release of a synaptic vesicle. The vesicle contains neurotransmitters that then cross the synaptic cleft and are converted into an electrical signal in the postsynaptic cell through opening of neurotransmitter-gated ion channels. This complicated chemical process underlies all communication in the nervous system and presumably evolved to allow sophisticated modulation of synaptic connections, since electrical connections consisting of gap-junctions would be sufficient to just transmit the electrical signal. One of the ways this process is regulated is whether or not the action potential causes release of a synaptic vesicle. The ability to modulate the probability of transmitter release underlies much of the plasticity of the nervous system. In our program, we will elucidate fundamental mechanisms by which release is regulated using the model sensory-motor neuron synapse of the marine snail Aplysia. In this animal, behavioral habituation, the ability of the animal to ignore innocuous stimuli, is mediated by the loss of transmitter release at this synapse. A noxious stimulus, through the release of serotonin, leads both to the reversal of habituation (through regaining transmitter release at the synapse) and sensitization, through increasing transmitter release at this synapse. The modulation of these synapses can be studied in cultures, where molecular and cellular techniques can be applied to determine the mechanisms by which this regulation is mediated. This will lead to fundamental discoveries on how transmitter release is regulated and thus how synapses work.

神经元之间通过突触进行交流。当动作电位到达突触的突触前一侧时，电信号通过突触小泡的钙依赖释放转化为化学信号。囊泡含有神经递质，然后穿过突触裂隙，通过打开神经递质门控离子通道，在突触后细胞中转化为电信号。这一复杂的化学过程是神经系统所有通讯的基础，并可能进化为允许对突触连接进行复杂的调制，因为由缝隙连接组成的电连接足以传递电信号。调控这一过程的方法之一是，动作电位是否会导致突触小泡的释放。调节递质释放概率的能力是神经系统的大部分可塑性的基础。在我们的节目中，我们将利用海洋蜗牛海兔的感觉-运动神经元突触模型来阐明调节释放的基本机制。在这种动物中，行为习惯化，即动物忽视无害刺激的能力，是通过在这个突触失去递质释放来调节的。有害的刺激通过释放5-羟色胺，导致习惯性的逆转(通过在突触重新释放递质)和敏化，通过增加突触的递质释放。这些突触的调节可以在培养中进行研究，在那里可以应用分子和细胞技术来确定这种调节的调节机制。这将导致对递质释放如何调控以及突触如何工作的基础性发现。