Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
基本信息
- 批准号:RGPIN-2019-03951
- 负责人:
- 金额:$ 4.23万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Neurons communicate through synaptic connections and these synapses underlie most brain function. At synapses, the presynaptic cell releases neurotransmitter though calcium-dependent release of synaptic vesicles that contain the neurotransmitters. The post-synaptic cell then responds through neurotransmitter-gated ion channels. Importantly, many synaptic connections are specialized for specific brain functions and control transmitter release in unique ways. The synaptic connections between the sensory neuron and the motor neuron that underlie the simple defensive withdrawal reflexes of the marine mollusc Aplysia californica have long been used to study the mechanisms underlying the control of synaptic transmission. The reflexes habituate with repeated activation through reducing release of the neurotransmitter-containing synaptic vesicles at the sensory-to-motor neuron synapses, termed homosynaptic depression. The sensory neurons must have specializations that mediate this depression, since most synapses do not decrease their release of synaptic vesicles under these conditions. A noxious stimulus to the animal results in the recovery from depression and behavioral dishabituation of the reflexes. The reduction in transmitter release during homosynaptic depression is known to involve changes in the efficacy of calcium to trigger the release of neurotransmitter: a change in calcium-secretion coupling. However, the molecular mechanisms of both homosynaptic depression and how it is reversed remain unknown. Evidence from a wide variety of synapses suggests calcium-secretion coupling is regulated through interactions between the specific calcium channel, CaV2, the source of calcium that triggers neurotransmitter release, and the synaptic vesicle. In the present application we will examine whether different sensory neuron-specific modifications of CaV2 or of the proteins that link CaV2 to the synaptic vesicles underlie homosynaptic depression and its reversal. We will measure depression and its reversal at sensory-motor neuron synapses where the sensory neurons express a modified CaV2 that either lacks sensory-neuron specific splicing, or specific binding sites for proteins important for interacting with synaptic vesicles. We will also examine the effects of expressing proteins that link CaV2 to synaptic vesicles that are not normally expressed in sensory neurons. These experiments will identify why sensory neurons depress and how the reversal of depression is mediated. These results will determine how transmitter release is regulated at this specialized synapse and provide general answers to the question of how calcium-secretion coupling functions and how transmitter release can be specialized at specific synapses in order to optimize brain function.
神经元通过突触连接进行交流,这些突触构成了大部分大脑功能的基础。在突触,突触前细胞通过钙依赖地释放包含神经递质的突触小泡来释放神经递质。然后,突触后细胞通过神经递质门控离子通道做出反应。重要的是,许多突触连接专用于特定的大脑功能,并以独特的方式控制递质释放。感觉神经元和运动神经元之间的突触联系是海洋软体动物海兔简单的防御性撤退反射的基础,长期以来一直被用来研究突触传递的控制机制。这些反射通过减少感觉-运动神经元突触上含有神经递质的突触小泡的释放而习惯性地重复激活,称为同型突触抑制。感觉神经元必须有调节这种抑制的特化,因为在这种情况下,大多数突触不会减少突触小泡的释放。对动物的有害刺激会导致动物从抑郁中恢复过来,并导致反射的行为不适应。在同型突触抑制期间递质释放的减少被认为涉及钙触发神经递质释放的有效性的变化:钙-分泌偶联的变化。然而,同型突触抑制的分子机制及其如何逆转仍不清楚。来自多种突触的证据表明,钙-分泌耦合是通过特定的钙通道CaV2和突触小泡之间的相互作用来调节的。CaV2是触发神经递质释放的钙源。在目前的应用中,我们将研究CaV2或将CaV2连接到突触小泡的蛋白质的不同感觉神经元特异性修饰是否导致同种突触抑制及其逆转。我们将测量感觉运动神经元突触的抑制及其逆转,其中感觉神经元表达修饰的CaV2,该修饰的CaV2要么缺乏感觉神经元特异性剪接,要么缺乏与突触小泡相互作用的重要蛋白质的特定结合位点。我们还将研究将CaV2连接到突触小泡的表达蛋白的影响,这些蛋白通常不在感觉神经元中表达。这些实验将确定感觉神经元为什么会抑郁,以及抑郁症的逆转是如何介导的。这些结果将确定递质释放是如何在这个专门的突触调节的,并为钙分泌偶联功能如何发挥作用以及如何在特定突触专门化递质释放以优化大脑功能的问题提供一般性答案。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sossin, Wayne其他文献
Sossin, Wayne的其他文献
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{{ truncateString('Sossin, Wayne', 18)}}的其他基金
Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
- 批准号:
RGPIN-2019-03951 - 财政年份:2021
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
- 批准号:
RGPIN-2019-03951 - 财政年份:2020
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
- 批准号:
RGPIN-2019-03951 - 财政年份:2019
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Regulation of calcium-secretion coupling
钙分泌偶联的调节
- 批准号:
171404-2011 - 财政年份:2017
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Regulation of calcium-secretion coupling
钙分泌偶联的调节
- 批准号:
171404-2011 - 财政年份:2016
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Regulation of calcium-secretion coupling
钙分泌偶联的调节
- 批准号:
171404-2011 - 财政年份:2015
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Regulation of calcium-secretion coupling
钙分泌偶联的调节
- 批准号:
171404-2011 - 财政年份:2014
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Regulation of calcium-secretion coupling
钙分泌偶联的调节
- 批准号:
171404-2011 - 财政年份:2013
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Regulation of calcium-secretion coupling
钙分泌偶联的调节
- 批准号:
171404-2011 - 财政年份:2012
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Regulation of calcium-secretion coupling
钙分泌偶联的调节
- 批准号:
171404-2011 - 财政年份:2011
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
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Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
- 批准号:
562270-2021 - 财政年份:2021
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Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
- 批准号:
RGPIN-2019-03951 - 财政年份:2021
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
- 批准号:
RGPIN-2019-03951 - 财政年份:2020
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
Role of the CaV2 channel in regulating transmitter release in Aplysia sensory neurons
CaV2 通道在调节海兔感觉神经元递质释放中的作用
- 批准号:
RGPIN-2019-03951 - 财政年份:2019
- 资助金额:
$ 4.23万 - 项目类别:
Discovery Grants Program - Individual
The function of presynaptic Cav2 Ca2+ channels (A01)
突触前 Cav2 Ca2 通道的功能 (A01)
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62174684 - 财政年份:2008
- 资助金额:
$ 4.23万 - 项目类别:
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