Multivesicular synaptic release

多泡突触释放

• 批准号: 7094178
• 负责人: CRAIG E JAHR
• 金额: $ 26.97万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094178
• 关键词: action potentials; cell cell interaction; electrophysiology; intercellular connection; laboratory rat; neural plasticity; neural transmission; neuromuscular transmission; neurotransmitter transport; synapses

DESCRIPTION (provided by applicant): Cell-to-cell transmission of information in the CNS is thought to occur at individual synapses, isolated from their neighbors. However, phenomena such as transmitter spillover and pooling between synapses have suggested that point-to-point synaptic communication between neurons is not the only method of information transfer in the CNS. Whether spillover and pooling of transmitter occurs depends on several variables including the amount of transmitter released per synapse per presynaptic action potential. If clearance mechanisms are overwhelm by release, transmitter will spread away from synapses. At some synapses, manipulations that increase the probability of vesicular release result in the release of multiple vesicles from individual synapses following single presynaptic action potentials. This large bolus of transmitter can overwhelm local transporters and result in spillover. At other synapses, however, multivesicular release has not been found regardless of the release probability suggesting that there is a mechanism that prevents release of more than a single vesicle. Transmitter spillover and pooling are at least in part responsible for activation of extrasynaptic receptors including metabotropic receptors which in turn are required for several types of short and long term plasticity. The main objectives of this proposal are to determine the extent to which plasticity depends on transmitter spillover and the degree to which spillover depends on multivesicular release. This will be accomplished using a combination of electrophysiological and optical techniques in the study of three different synapses each with distinct characteristics. The plan is to use the attributes of each of these synapses to probe, first, the generality of multivesicular release and, second, the multiplicity of its consequences. All CNS functions including sensory processing, motor behavior, consciousness, and memory depend on intact synaptic transmission. Knowledge of the fundamental molecular and cellular properties of transmission is required for the development of rational interventions in pathological states.

描述（由申请人提供）：中枢神经系统中信息传输被认为是在与邻居隔离的单个突触中发生的。但是，诸如发射器溢出和突触之间的合并之类的现象表明，神经元之间的点对点突触通信不是中枢神经系统中信息传输的唯一方法。发射机的溢出和合并是否取决于几个变量，包括每次突触前动作电位每次突触释放的发射机量。如果清除机制因释放而淹没，发射器将脱离突触。在某些突触中，增加囊泡释放概率的操作会导致在单个突触前作用电位后从单个突触中释放多个囊泡。这种大的发射器推注会使本地转运蛋白淹没并导致溢出。然而，在其他突触下，无论释放概率是否表明有一种机制可以防止释放不仅仅是单个囊泡，尚未发现多个释放。发射机溢出和合并至少部分负责激活包括代谢型受体，而这些受体又需要几种类型的短期和长期可塑性。该提案的主要目的是确定可塑性取决于发射机溢出的程度以及溢出依赖多重释放的程度。这将在三种不同特征的三种突触研究中使用电生理学和光学技术的组合来实现。该计划是使用这些突触的每一个的属性进行探测，首先是多源释放的一般性，其次是其后果的多样性。所有中枢神经系统的功能，包括感觉处理，运动行为，意识和记忆都取决于完整的突触传播。需要了解传播的基本分子和细胞特性才能发展病理状态的理性干预措施。