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Cell-Contact Mediated Mechanisms Assembling Synapses

细胞接触介导的突触组装机制

基本信息

批准号：
10307078
负责人：
Matthew B Dalva
金额：
$ 42.41万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10307078
关键词：
Addictive Behavior Address Alzheimer&apos s Disease Architecture Area Brain Cells Cellular Morphology Chemicals Color Communication Data Defect Dendritic Spines Disease Ephrin-B3 Epilepsy Event Generations Glutamate Receptor Health Human Image Label Learning Link Logic Maintenance Mediating Methods Microscopy Molecular Morphology NMDA receptor A1 Nervous system structure Neurons Pain Pathologic Pathology Pattern Presynaptic Terminals Process Proteins Research Resolution Scaffolding Protein Shapes Site Societies Structure Synapses Synaptic Transmission Synaptic plasticity Synaptophysin Testing Vertebral column addiction autism spectrum disorder base bassoon protein density developmental disease experience experimental study insight molecular dynamics nano nanoarchitecture nanoscale neural circuit neurotransmitter release novel painful neuropathy postsynaptic postsynaptic density protein presynaptic presynaptic density protein 95 reconstruction synaptogenesis synaptotagmin I synaptotagmin VII

项目摘要

Formation and plasticity of synapses are essential for normal functioning of the brain and key events for learning and adaptive plasticity. Diseases such as addiction, epilepsy, and Alzheimer's that involve maladaptive plasticity appear to highjack these same mechanisms controlling these events leading to disease states. The area of addition is particular pressing given the devastating impact the disease has on society and the clear like between addictive behaviors and the formation of new synapses and/or maladaptive plastic changes in the brain. Therefore, understanding the mechanisms that regulate normal develop and plasticity in the brain are likely to be critical for any advances in treatment of these diseases. The majority of synaptic contacts that form are made on dendritic spines, which are also a key site of synaptic plasticity. Dendritic spines contain specialized structures called postsynaptic densities (PSDs) that are directly apposed to pre-synaptic neurotransmitter release sites and which scale in size with changes in synaptic strength. Despite having understood this relationship for many years, the molecular dynamics of the translocation and accumulation of PSD proteins and presynaptic proteins following structural plasticity remain poorly understood. Our preliminary data indicate that pre- and postsynaptic proteins for scale in a modular fashion with dendritic spine size. We will determine the synaptic molecular architecture and address how the molecular architecture of the spine synapse responds to structural plasticity in three aims: 1) Determine the nanoarchitecture of glutamate receptors at spine synapses. 2) Determine the nanoscale organization of synchronous and asynchronous synaptic release sites. 3) Determine how PSD-95 nanomodule number and plasticity are regulated. Collectively these studies will advance our understand of basic mechanisms that impact the ability of the nervous system to grow and change, events that are likely central to disease of maladaptive plasticity such as addiction and Alzheimer's.

突触的形成和可塑性对大脑的正常功能至关重要

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Ephecting excitatory synapse development.

DOI：
10.1016/j.cell.2010.10.017
发表时间：
2010-10-29
期刊：
Cell
影响因子：
64.5
作者：
Dalva MB
通讯作者：
Dalva MB

Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3.

DOI：
10.1038/nn.4140
发表时间：
2015-11
期刊：
Nature neuroscience
影响因子：
25
作者：
Hruska M;Henderson NT;Xia NL;Le Marchand SJ;Dalva MB
通讯作者：
Dalva MB

Neuronal activity moves protein palmitoylation into the synapse.

DOI：
10.1083/jcb.200906101
发表时间：
2009-07-13
期刊：
The Journal of cell biology
影响因子：
0
作者：
Dalva MB
通讯作者：
Dalva MB

Ephrin regulation of synapse formation, function and plasticity.

DOI：
10.1016/j.mcn.2012.03.004
发表时间：
2012-05
期刊：
Molecular and cellular neurosciences
影响因子：
0
作者：
Hruska M;Dalva MB
通讯作者：
Dalva MB

EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner.

DOI：
10.1523/jneurosci.0282-11.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Nolt MJ;Lin Y;Hruska M;Murphy J;Sheffler-Colins SI;Kayser MS;Passer J;Bennett MV;Zukin RS;Dalva MB
通讯作者：
Dalva MB