Timing of Neurotransmitter Release

神经递质释放的时机

• 批准号: 7696059
• 负责人: Jacques Wadiche
• 金额: $ 32.01万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7696059
• 关键词: Action Potentials; Acute; Address; Affinity; Area; Basic Science; Behavior; Brain; Brain Diseases; Calcium; Calcium Channel; Cells; Communication; Complex; Dendrites; Diffusion; Electrophysiology (science); Ensure; Event; Failure; Fiber; Frequencies; Glutamates; Goals; Image; Individual; Ion Pumps; Kinetics; Lead; Learning Disorders; Memory; Mus; Nerve; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neuroglia; Neurons; Neurosciences; Neurotransmitters; Output; Pattern; Pharmacology; Physiological; Play; Preparation; Presynaptic Receptors; Presynaptic Terminals; Probability; Process; Purkinje Cells; Receptor Activation; Recording of previous events; Regulation; Relative (related person); Role; Shapes; Signal Transduction; Site; Slice; Speed; Staging; Stimulus; Synapses; Synaptic Receptors; Synaptic Transmission; Synaptic plasticity; Testing; Time; Vesicle; Work; base; clinically relevant; desensitization; insight; millisecond; motor control; motor disorder; motor learning; neurotransmitter release; postsynaptic; presynaptic; public health relevance; relating to nervous system; response; synaptic function; transmission process; voltage

DESCRIPTION (provided by applicant): Brain function relies on information transfer between neurons at structurally and functionally defined sites called synapses. Considerable effort is directed at understanding the detailed mechanisms underlying synaptic transmission because it is increasingly clear that many diseases of the brain, including neurodevelopmental disorders and the earliest stages of neurodegenerative diseases, are associated with dysregulation of synaptic function. Synaptic transmission is composed of three components including the presynaptic release of neurotransmitter containing vesicles, diffusion of neurotransmitter through the space between neurons, and the activation of receptors that generate a response in the postsynaptic neuron. These events take place on a millisecond time scale, and the timing of each component is tightly controlled to ensure precise and efficient information transfer. Yet transmission is also highly dynamic, showing many types of plasticity in response to natural stimulus patterns. The overall goal of this project is to determine how activity controls the synchrony of neurotransmitter release from the presynaptic terminal, and how this activity-dependent plasticity contributes to the timing of information transfer through the synapse. We will first establish the conditions and mechanisms that control the synchronicity of transmitter release. We will subsequently test physiological consequences of activity dependent asynchronous transmitter release in terms of neural output and postsynaptic Ca2+ signaling. These studies will be conducted in brain slices from mice using voltage and current clamp recordings as well as calcium imaging and pharmacological manipulations. We will use a cerebellar synapse where it is well established that precise timing of synaptic transmission is critical for behaviors such as motor control and motor learning. The results from these studies will provide insight into an important presynaptic mechanism for regulating synaptic transmission that likely plays a role in neural timing throughout the CNS. PUBLIC HEALTH RELEVANCE: The timing of fast synaptic transmission is tightly controlled to ensure precise and efficient information transfer. The overall goal of this project is to determine how activity controls the synchrony of neurotransmitter release from the presynaptic terminal, and how this contributes to the timing of information transfer through the synapse.

描述（由申请人提供）：大脑功能依赖于在结构和功能定义的位点上称为突触的神经元之间的信息传递。大量努力旨在理解突触传播的详细机制，因为越来越明显的是，包括神经发育疾病在内的许多大脑疾病和神经退行性疾病的最早疾病都与突发功能的失调有关。突触传播由三个组成部分组成，包括含有囊泡的神经递质的突触前释放，神经递质通过神经元之间的空间扩散以及受体的激活，这些受体激活在突触后神经元中产生反应。这些事件以毫秒的时间范围进行，并且每个组件的时间安排受到严格控制，以确保精确有效的信息传输。然而，传播也是高度动态的，显示出许多类型的可塑性，以响应自然刺激模式。该项目的总体目标是确定活动如何控制神经递质从突触前终端释放的同步，以及该活动依赖性可塑性如何有助于通过突触传递信息的时间。我们将首先建立控制发射器释放同步性的条件和机制。随后，我们将根据神经输出和突触后CA2+信号传导的活性依赖性异步发射器释放的生理后果。这些研究将使用电压和当前夹具记录以及钙成像和药理学操纵在小鼠的脑切片中进行。我们将使用小脑突触，可以很好地确定突触传播的精确时机对于诸如运动控制和运动学习等行为至关重要。这些研究的结果将为调节突触传播的重要前机制提供洞察力，该机制可能在整个中枢神经系统的神经时机中起作用。公共卫生相关性：紧密控制快速突触传输的时间，以确保精确有效的信息传输。该项目的总体目标是确定活动如何控制神经递质从突触前终端释放的同步，以及这如何有助于通过突触传递信息的时间。