Neurodevelopmental Disorder Risk Gene Regulation of Intrinsic Membrane Excitability: A Rheostat that Tunes Dendritic Morphogenesis to Regulate Circuit Assembly During Development
内在膜兴奋性的神经发育障碍风险基因调节:调节树突形态发生以调节发育过程中电路组装的变阻器
基本信息
- 批准号:10571558
- 负责人:
- 金额:$ 67.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AreaBasic ScienceBehaviorBehavioralBiological ProcessBrainBrain DiseasesCandidate Disease GeneCellsCerebral cortexChildhoodDataDecision MakingDevelopmentDiseaseEtiologyGene ExpressionGene Expression RegulationGenesGeneticGlutamatesGoalsHumanImageImpaired cognitionImpairmentIon ChannelKv4 channelLearningLinkMediatingMembraneMolecularMorphogenesisMusNeurobiologyNeurodevelopmental DisorderNeuronsOrganPathway interactionsPerceptionPerceptual learningPerinatalPeripheralPotassium ChannelProcessProtein IsoformsProteinsRNA SplicingRegulationResearchResearch DesignRoleSYNGAP1SensoryShapesSignal TransductionSomatosensory CortexStructureSurfaceSynapsesTestingThinkingTouch sensationVibrissaeWorkautisticbehavioral impairmentcognitive abilitycognitive functioncognitive processcourse developmentexcitatory neurongene functionin vivoinsightloss of functionmaladaptive behaviorneural circuitneurophysiologynovelrelating to nervous systemresponserisk variantsensory cortextooltwo-photon
项目摘要
Project Summary
The goal of this project is to understand how gene expression during development shapes the delicate and
massively parallel cell biological processes that promote wiring of functional networks within the cerebral
cortex. This is an important area of basic research because neural dynamics within cortical networks are the
direct correlates of thought and behavior. These cognitive processes emerge as neural circuits form through
expression of genes over the course of development. Moreover, cognitive impairment, which defines
neurodevelopmental disorders (NDDs), is thought to arise, at least in part, from impaired neural circuit
connectivity within the developing cortex. A revelation over the past decade is that NDDs can be caused by de
novo genetic loss-of-function SNVs within a single gene. Thus, in-depth study of natural functions of these
genes can reveal the neurobiological principles underlying the typically developing cortex and as well as
principles that contribute to abnormal cortical development associated with NDDs. In this project, we will
explore the hypothesis that expression of NDD-associated genes in the typically developing cortex promotes
the assembly of cortical circuits through cell-autonomous regulation of intrinsic membrane excitability. This
hypothesis is significant because it is known that neural activity shapes the assembly of developing cortical
circuits. However, it remains unknown how genes function at the cellular level to promote activity-dependent in
vivo development of cortical circuit motifs known to promote cognitive function and behavioral adaptations. Aim
1 will explore the causal relationships between genetic control of intrinsic membrane excitability (IME), activity-
dependent dendritic morphogenesis, and developmental assembly of cortical circuits. Aim 2 will explore causal
links between genetic control of IME, neuronal ensemble structure/function, and behavioral adaptations. We
will do this by regulating genetic control of IME in developing cortical neurons and then observing the effect of
this on cortical ensembles and behavioral adaptions. This research design is important because the brain
functions across multiple temporal and spatial scales – indeed, this project attempts to link gene function
across the major levels of brain function – gene>neuron>synapse>circuit>ensemble>behavior. The overall
impact of this proposed research is that it has the potential to reveal how gene expression shapes the activity-
dependent assembly of neural circuits that promote cognitive functions required for behavioral adaptations.
Because we focus on natural functions of an NDD gene, these basic insights are also directly relatable to the
etiology of cortical wiring impairments associated with childhood brain disorders.
Project Summary
The goal of this project is to understand how gene expression during development shapes the delicate and
massively parallel cell biological processes that promote wiring of functional networks within the cerebral
cortex. This is an important area of basic research because neural dynamics within cortical networks are the
direct correlates of thought and behavior. These cognitive processes emerge as neural circuits form through
expression of genes over the course of development. Moreover, cognitive impairment, which defines
neurodevelopmental disorders (NDDs), is thought to arise, at least in part, from impaired neural circuit
connectivity within the developing cortex. A revelation over the past decade is that NDDs can be caused by de
novo genetic loss-of-function SNVs within a single gene. Thus, in-depth study of natural functions of these
genes can reveal the neurobiological principles underlying the typically developing cortex and as well as
principles that contribute to abnormal cortical development associated with NDDs. In this project, we will
explore the hypothesis that expression of NDD-associated genes in the typically developing cortex promotes
the assembly of cortical circuits through cell-autonomous regulation of intrinsic membrane excitability. This
hypothesis is significant because it is known that neural activity shapes the assembly of developing cortical
circuits. However, it remains unknown how genes function at the cellular level to promote activity-dependent in
vivo development of cortical circuit motifs known to promote cognitive function and behavioral adaptations. Aim
1 will explore the causal relationships between genetic control of intrinsic membrane excitability (IME), activity-
dependent dendritic morphogenesis, and developmental assembly of cortical circuits. Aim 2 will explore causal
links between genetic control of IME, neuronal ensemble structure/function, and behavioral adaptations. We
will do this by regulating genetic control of IME in developing cortical neurons and then observing the effect of
this on cortical ensembles and behavioral adaptions. This research design is important because the brain
functions across multiple temporal and spatial scales – indeed, this project attempts to link gene function
across the major levels of brain function – gene>neuron>synapse>circuit>ensemble>behavior. The overall
impact of this proposed research is that it has the potential to reveal how gene expression shapes the activity-
dependent assembly of neural circuits that promote cognitive functions required for behavioral adaptations.
Because we focus on natural functions of an NDD gene, these basic insights are also directly relatable to the
etiology of cortical wiring impairments associated with childhood brain disorders.
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 }}
GAVIN R RUMBAUGH其他文献
GAVIN R RUMBAUGH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('GAVIN R RUMBAUGH', 18)}}的其他基金
Molecular and cellular basis for autism spectrum disorders caused by exacerbated translation
加剧翻译引起的自闭症谱系障碍的分子和细胞基础
- 批准号:
10697387 - 财政年份:2022
- 资助金额:
$ 67.84万 - 项目类别:
Molecular and cellular basis for autism spectrum disorders caused by exacerbated translation
加剧翻译引起的自闭症谱系障碍的分子和细胞基础
- 批准号:
10704718 - 财政年份:2022
- 资助金额:
$ 67.84万 - 项目类别:
Molecular and cellular basis for autism spectrum disorders caused by exacerbated translation
加剧翻译引起的自闭症谱系障碍的分子和细胞基础
- 批准号:
10456979 - 财政年份:2022
- 资助金额:
$ 67.84万 - 项目类别:
Molecular and cellular basis for autism spectrum disorders caused by exacerbated translation
加剧翻译引起的自闭症谱系障碍的分子和细胞基础
- 批准号:
10264087 - 财政年份:2020
- 资助金额:
$ 67.84万 - 项目类别:
Causal Interactions between genetic risk, precise cortical connectivity, and autism-associated behaviors
遗传风险、精确皮质连接和自闭症相关行为之间的因果相互作用
- 批准号:
10526411 - 财政年份:2019
- 资助金额:
$ 67.84万 - 项目类别:
Causal Interactions between genetic risk, precise cortical connectivity, and autism-associated behaviors
遗传风险、精确皮质连接和自闭症相关行为之间的因果相互作用
- 批准号:
9885217 - 财政年份:2019
- 资助金额:
$ 67.84万 - 项目类别:
Causal Interactions between genetic risk, precise cortical connectivity, and autism-associated behaviors
遗传风险、精确皮质连接和自闭症相关行为之间的因果相互作用
- 批准号:
10616304 - 财政年份:2019
- 资助金额:
$ 67.84万 - 项目类别:
Causal Interactions between genetic risk, precise cortical connectivity, and autism-associated behaviors
遗传风险、精确皮质连接和自闭症相关行为之间的因果相互作用
- 批准号:
10063962 - 财政年份:2019
- 资助金额:
$ 67.84万 - 项目类别:
Causal Interactions between genetic risk, precise cortical connectivity, and autism-associated behaviors
遗传风险、精确皮质连接和自闭症相关行为之间的因果相互作用
- 批准号:
10307109 - 财政年份:2019
- 资助金额:
$ 67.84万 - 项目类别:
A Scalable Neuron-Based High-Throughput Screening Platform for the Discovery of Compounds that Restore Protein Expression Caused by Genetic Haploinsufficiency
一种可扩展的基于神经元的高通量筛选平台,用于发现可恢复由遗传单倍体不足引起的蛋白质表达的化合物
- 批准号:
9370360 - 财政年份:2017
- 资助金额:
$ 67.84万 - 项目类别:
相似海外基金
HNDS-R: Connectivity, Inclusiveness, and the Permeability of Basic Science
HNDS-R:基础科学的连通性、包容性和渗透性
- 批准号:
2318404 - 财政年份:2023
- 资助金额:
$ 67.84万 - 项目类别:
Standard Grant
Advancing the basic science of membrane permeability in macrocyclic peptides
推进大环肽膜渗透性的基础科学
- 批准号:
10552484 - 财政年份:2023
- 资助金额:
$ 67.84万 - 项目类别:
Computer Vision for Malaria Microscopy: Automated Detection and Classification of Plasmodium for Basic Science and Pre-Clinical Applications
用于疟疾显微镜的计算机视觉:用于基础科学和临床前应用的疟原虫自动检测和分类
- 批准号:
10576701 - 财政年份:2023
- 资助金额:
$ 67.84万 - 项目类别:
Bringing together communities and basic science researchers to build stronger relationships
将社区和基础科学研究人员聚集在一起,建立更牢固的关系
- 批准号:
480914 - 财政年份:2023
- 资助金额:
$ 67.84万 - 项目类别:
Miscellaneous Programs
“L-form” bacteria: basic science, antibiotics, evolution and biotechnology
L 型细菌:基础科学、抗生素、进化和生物技术
- 批准号:
FL210100071 - 财政年份:2022
- 资助金额:
$ 67.84万 - 项目类别:
Australian Laureate Fellowships
Coordinating and Data Management Center for Translational and Basic Science Research in Early Lesions
早期病变转化和基础科学研究协调和数据管理中心
- 批准号:
10517004 - 财政年份:2022
- 资助金额:
$ 67.84万 - 项目类别:
Developing science communication on large scale basic science represented by accelerator science
发展以加速器科学为代表的大规模基础科学科学传播
- 批准号:
22K02974 - 财政年份:2022
- 资助金额:
$ 67.84万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Basic Science Core - Biosafety & Biocontainment Core (BBC)
基础科学核心 - 生物安全
- 批准号:
10431468 - 财政年份:2022
- 资助金额:
$ 67.84万 - 项目类别: