Single synapse analysis of synaptic plasticity by combining electrophysiology and array tomography

结合电生理学和阵列断层扫描的突触可塑性单突触分析

• 批准号: 10059263
• 负责人: Vernon Daniel MADISON
• 金额: $ 56.57万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-23 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059263
• 关键词: AMPA Receptors; Affect; Amino Acid Sequence; Anatomy; Array tomography; Binding; Brain; C-terminal; Cells; Chemosensitization; DLG4 gene; Data; Dendritic Spines; Destinations; Diffusion; Electric Stimulation; Electrophysiology (science); Environment; Glutamate Receptor; Grant; Investigation; Knowledge; Learning; Location; Long-Term Depression; Long-Term Potentiation; Membrane; Mental Depression; Modeling; Movement; Nature; Neurons; Pathology; Pattern; Peptides; Physiological; Play; Postsynaptic Membrane; Process; Property; Proteins; Role; Series; Site; Sorting - Cell Movement; Surface; Surveys; Synapses; Synaptic plasticity; Tail; Techniques; Testing; Time; Vertebral column; density; design; experimental study; functional disability; hippocampal pyramidal neuron; peptidomimetics; postsynaptic; postsynaptic neurons; receptor; tomography; trafficking

The most well-established mechanism for the expression of the activity-dependent forms of synaptic plasticity known as long-term potentiation (LTP) and long-term depression (LTD) is the trafficking of AMPA receptors (AMPARs) into or out of the postsynaptic membrane. This trafficking is believed to be shaped in important ways by the identity of the particular receptor subunits present in the dendritic spine. The dominant model of AMPAR trafficking has held that the unique C-terminal tails of these subunits play an important role in sorting these receptors to their intended destination, whether it be in the surface membrane, specifically in the postsynaptic membrane, or at an intracellular site. Recently that model has been partly challenged by findings that suggest that AMPARs are not sorted by subunit composition, but rather that the primary driver of LTP induction is a change in the properties of the postsynaptic density and/or in dendritic spine volume that captures additional AMPARs in a subunit indiscriminate manner. Yet at the same time, previous data, including our own, strongly support the idea that specific AMPAR subunits in the postsynaptic membrane are crucial for the induction of LTP and the specification of defined synaptic plasticity states. This grant seeks to leverage the existing knowledge about the trafficking of AMPA receptors in a new series of experiments that combines our established techniques of paired-neuron electrophysiological recordings with our more recently acquired ability to use array tomography to track the location of glutamate receptor subunits on dendritic spines of synapses specifically known to have undergone plasticity. We will test competing hypotheses concerning the nature of AMPA receptor trafficking into postsynaptic membranes during the induction of synaptic plasticity.

最完善的表达活性依赖性形式的机制， 突触可塑性被称为长时程增强（LTP）和长时程抑制（LTD）， AMPA受体（AMPAR）进出突触后膜的运输。这 贩运被认为是由特定受体的身份在重要方面形成的 亚基存在于树突棘中。AMPAR贩运的主要模式认为， 这些亚基的独特C末端尾在将这些受体分类中起重要作用， 它们的预期目的地，无论是在表面膜，特别是在 突触后膜，或在细胞内的网站。最近，这种模式部分地 挑战的发现表明，AMPAR不是由亚基组成排序，但 相反，LTP诱导的主要驱动因素是突触后神经元特性的变化。 密度和/或树突棘体积，其在亚基中捕获额外的AMPAR 不分青红皂白的方式。然而，与此同时，包括我们自己在内的先前数据强烈支持 突触后膜中的特定AMPAR亚基对于突触后膜的形成至关重要， LTP的诱导和定义的突触可塑性状态的规范。该补助金旨在 利用现有的知识贩运AMPA受体在一个新的系列， 结合我们建立的配对神经元电生理学技术的实验 记录与我们最近获得的能力，使用阵列层析成像跟踪的位置， 突触树突棘上的谷氨酸受体亚单位， 经历了可塑性。我们将测试有关AMPA性质的竞争性假设 在突触可塑性的诱导过程中，受体向突触后膜的运输。

项目成果

Disruption of circadian timing increases synaptic inhibition and reduces cholinergic responsiveness in the dentate gyrus.

• DOI: 10.1002/hipo.23301
• 发表时间: 2021-04
• 期刊: Hippocampus
• 影响因子: 3.5
• 作者: McMartin L;Kiraly M;Heller HC;Madison DV;Ruby NF
• 通讯作者: Ruby NF

Array tomography of physiologically-characterized CNS synapses.

• DOI: 10.1016/j.jneumeth.2016.04.017
• 发表时间: 2016-08-01
• 期刊: Journal of neuroscience methods
• 影响因子: 3
• 作者: Valenzuela RA;Micheva KD;Kiraly M;Li D;Madison DV
• 通讯作者: Madison DV

Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome.

脆性 X 综合征小鼠模型中突触组成和星形胶质细胞参与的多方面变化。

• DOI: 10.1038/s41598-019-50240-x
• 发表时间: 2019
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Simhal,AnishK;Zuo,Yi;Perez,MarcM;Madison,DanielV;Sapiro,Guillermo;Micheva,KristinaD
• 通讯作者: Micheva,KristinaD

Extensive Structural Remodeling of the Axonal Arbors of Parvalbumin Basket Cells during Development in Mouse Neocortex.

小鼠新皮质发育过程中小清蛋白篮细胞轴突轴突的广泛结构重塑。

• DOI: 10.1523/jneurosci.0871-21.2021
• 发表时间: 2021
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Micheva,KristinaD;Kiraly,Marianna;Perez,MarcM;Madison,DanielV
• 通讯作者: Madison,DanielV