Strategy to map electrical synaptic connectivity in neural networks
映射神经网络中电突触连接的策略
基本信息
- 批准号:10285599
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-15 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAlgorithmsAntibody Binding SitesAreaBRAIN initiativeBehaviorBinding ProteinsBrainBrain DiseasesBrain regionCellsConfocal MicroscopyConnexinsConnexonCoupledCouplingDataData SetDegenerative DisorderDevelopmentDiagnosticElectrical SynapseElectron MicroscopyElectrophysiology (science)ElementsEnsureFosteringFunding OpportunitiesGap JunctionsHealthHumanImageIndividualIonsIsometric ExerciseLabelLeadLocationMapsMeasurementMeasuresMediatingMembraneMethodsMissionModelingMorphologyMusNervous system structureNeuronsNoisePhysiologicalPhysiologyPrimatesProbabilityProcessPropertyProteinsProtocols documentationPublic HealthReportingResearchResearch DesignResolutionRetinaScanningShapesSignal TransductionStructureSumSynapsesTechniquesTimeTissuesUnited States National Institutes of Healthconnexin 36gap junction channelinsightlarge scale dataneural networknonhuman primatenovelnovel strategiespatch clampprogramsreconstructionresponsesuccesstool
项目摘要
SUMMARY
Electrical synapses, also known as gap junctions, occur frequently in all nervous systems, including the human
brain. They are composed of connexins, arranged to form intercellular channels between adjacent, coupled
cells. Connexin36 (Cx36) is the predominant connexin in the CNS. In many brain and retinal circuits, gap
junctions provide direct and specific connections between cells. In addition, electrical synapses mediate
network properties such as signal averaging, noise reduction and synchronization. However, because of their
small size, gap junctions are not visible in large-scale serial EM data sets. For these reasons, gap junctions
tend to be under-reported or simply ignored.
The objective of this proposal is to develop a combined approach to image gap junction connectivity in EM
datasets and, in addition, to estimate the size, strength, and plasticity of gap junctions. We will study regions of
the retina that contain gap junctions of dramatically different sizes and shapes, to allow us to correlate
structure and function. Aim 1 will use high-resolution confocal microscopy to determine connexon number at
large and small gap junctions. Analyses will determine the number of connexons per gap junction. These
methods will provide a general-purpose tool to determine the size of gap junctions for use in all brain regions.
Aim 2 will use 3D-EM imaging to allow unambiguous identification of gap junctions in FIB-SEM images, which
will follow with first-ever immunogold quantification of a membrane-bound protein in 3D-EM structures. These
studies will allow high-resolution quantification of gap junctions and proteins in identified neurons. Aim 3 will
use electrophysiological measures to determine coupling conductance and then develop models to calculate
the maximal potential coupling conductance from the morphological data by multiplying the number of
channels/gap junction [Specific Aim 1] times the connectivity (the number of gap junctions between coupled
cells) [Specific Aim 2], times the unitary conductance of Cx36. Using paired recordings, we will obtain direct
physiological measures of the junctional conductance between coupled cells. Then, by comparison with the
potential maximum calculated from the morphological data, we can calculate the open channel probability and
place realistic limits on the operating range. These are the fundamental properties required to understand the
function of gap junctions in neuronal microcircuits.
This program is an exact match for one of the listed areas, “Tools to identify gap junctions and characterize
electrical synapses” in the Funding Opportunity Announcement, RFA-MH-20-135.
摘要
电突触,也称为缝隙连接,在包括人类在内的所有神经系统中频繁出现。
大脑。它们由连接蛋白组成,排列成相邻的、耦合的细胞间通道
细胞。连接蛋白36(Cx36)是中枢神经系统中最主要的连接蛋白。在许多大脑和视网膜回路中,缝隙
连接提供了细胞之间的直接和特定的连接。此外,电突触在
网络属性,如信号平均、降噪和同步。然而,由于他们的
小尺寸、间隙连接在大规模连续EM数据集中不可见。出于这些原因,缝隙连接
往往被低估或干脆被忽视。
这项建议的目标是开发一种组合的方法来成像EM中的缝隙连接
此外,还可以评估缝隙连接的大小、强度和可塑性。我们将研究以下区域
视网膜包含大小和形状截然不同的缝隙连接,使我们能够相互联系
结构和功能。AIM 1将使用高分辨率共聚焦显微镜来确定连接子数
大缝隙和小缝隙连接。分析将确定每个缝隙连接的连接外显子的数量。这些
这些方法将提供一种通用的工具来确定所有大脑区域使用的缝隙连接的大小。
AIM 2将使用3D-EM成像来明确识别FIB-SEM图像中的缝隙连接,这
随后将首次对3D-EM结构中的膜结合蛋白进行免疫金定量。这些
研究将允许对已识别神经元中的缝隙连接和蛋白质进行高分辨率量化。目标3将
使用电生理测量来确定耦合电导,然后开发模型来计算
从形态数据乘以最大电势耦合电导
通道/缝隙连接[特定目标1]乘以连接性(耦合的缝隙连接的数量
细胞)[特定目标2],乘以Cx36的单位电导。使用配对录音,我们将直接获得
耦合细胞间连接电导的生理测量。然后,与
根据形态数据计算的势能极大值,我们可以计算明渠概率和
对工作范围设定现实的限制。这些是理解
缝隙连接在神经元微电路中的作用。
该程序与列出的其中一个领域完全匹配,即识别缝隙连接和特征的工具
电突触“在资助机会公告中,RFA-MH-20-135。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SUE A AICHER其他文献
SUE A AICHER的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SUE A AICHER', 18)}}的其他基金
Mechanisms of Pain and Photophobia in Migraine and Dry Eye
偏头痛和干眼症的疼痛和畏光机制
- 批准号:
10707192 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Mechanisms of Pain and Photophobia in Migraine and Dry Eye
偏头痛和干眼症的疼痛和畏光机制
- 批准号:
10583929 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Strategy to map electrical synaptic connectivity in neural networks
映射神经网络中电突触连接的策略
- 批准号:
10514909 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Tear protein biomarkers of refractive surgery pain
屈光手术疼痛的泪液蛋白生物标志物
- 批准号:
10707867 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Tear protein biomarkers of refractive surgery pain
屈光手术疼痛的泪液蛋白生物标志物
- 批准号:
10786192 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Tear protein biomarkers of refractive surgery pain
屈光手术疼痛的泪液蛋白生物标志物
- 批准号:
10062362 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Tear protein biomarkers of refractive surgery pain
屈光手术疼痛的泪液蛋白生物标志物
- 批准号:
10249335 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Psychostimulants induce long-term changes in nociception.
精神兴奋剂会引起伤害感受的长期变化。
- 批准号:
8511595 - 财政年份:2009
- 资助金额:
-- - 项目类别:
相似海外基金
DMS-EPSRC: Asymptotic Analysis of Online Training Algorithms in Machine Learning: Recurrent, Graphical, and Deep Neural Networks
DMS-EPSRC:机器学习中在线训练算法的渐近分析:循环、图形和深度神经网络
- 批准号:
EP/Y029089/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
CAREER: Blessing of Nonconvexity in Machine Learning - Landscape Analysis and Efficient Algorithms
职业:机器学习中非凸性的祝福 - 景观分析和高效算法
- 批准号:
2337776 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant
CAREER: From Dynamic Algorithms to Fast Optimization and Back
职业:从动态算法到快速优化并返回
- 批准号:
2338816 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant
CAREER: Structured Minimax Optimization: Theory, Algorithms, and Applications in Robust Learning
职业:结构化极小极大优化:稳健学习中的理论、算法和应用
- 批准号:
2338846 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant
CRII: SaTC: Reliable Hardware Architectures Against Side-Channel Attacks for Post-Quantum Cryptographic Algorithms
CRII:SaTC:针对后量子密码算法的侧通道攻击的可靠硬件架构
- 批准号:
2348261 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
CRII: AF: The Impact of Knowledge on the Performance of Distributed Algorithms
CRII:AF:知识对分布式算法性能的影响
- 批准号:
2348346 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
CRII: CSR: From Bloom Filters to Noise Reduction Streaming Algorithms
CRII:CSR:从布隆过滤器到降噪流算法
- 批准号:
2348457 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
EAGER: Search-Accelerated Markov Chain Monte Carlo Algorithms for Bayesian Neural Networks and Trillion-Dimensional Problems
EAGER:贝叶斯神经网络和万亿维问题的搜索加速马尔可夫链蒙特卡罗算法
- 批准号:
2404989 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
CAREER: Efficient Algorithms for Modern Computer Architecture
职业:现代计算机架构的高效算法
- 批准号:
2339310 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant
CAREER: Improving Real-world Performance of AI Biosignal Algorithms
职业:提高人工智能生物信号算法的实际性能
- 批准号:
2339669 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant