Biophysical and Circuit Mechanisms of OXTR signaling

OXTR信号的生物物理和电路机制

基本信息

  • 批准号:
    10438594
  • 负责人:
  • 金额:
    $ 40.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-15 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary (Project 3, Co-PIs: Tsien, Froemke, Buzsaki) Neuromodulators act across many timescales—a consequence of the dynamics of their release, receptor activation and downstream signaling. Their actions target numerous subcellular compartments, shaping synaptic transmission, intrinsic excitability and long-term plasticity. How, in turn, these phenomena translate to behavior is a fundamental goal of neuroscience research. In Project 3, we grapple with this complexity by deconstructing the actions of the peptide and hormone oxytocin. Famous for its roles in the periphery and in social behavior, the biophysical and cellular consequences of oxytocin signaling in the central nervous system are poorly described. A thorough understanding of how oxytocin’s role in the brain is further motivated by disruption of oxytocin signaling in various neuropsychiatric disorders, including ASD and schizophrenia. To address this gap in knowledge, we will study the cellular, synaptic and microcircuit signaling mechanisms of oxytocin in the hippocampus, focusing on the CA2 subregion. Long overlooked, CA2 is enriched in OXTRs and, intriguingly, has been implicated in social behavior. Our most recent efforts have focused on how activation of the OXTR depolarizes CA2 pyramidal cells and causes them to enter into a burst firing mode. This effect was attributable to inhibition of a Kv7-mediated potassium current (or M-current), downstream of a Gq- coupled signaling pathway. In Project 3, we take these biophysical results into increasingly more physiological contexts. In Aim 1, we ask how endogenous activity patterns of oxytocinergic fibers translate into oxytocin release, receptor activation and changes in intrinsic excitability. In Aim 2, we test the strength of our model (in which oxytocin’s effects in the hippocampus are primarily mediated by M-current inhibition), by developing optical tools that test the sufficiency and necessity of M-current inhibition in oxytocin signaling. In Aim 3, we ask how profound changes in hippocampal activity, specifically in CA2, are transmitted beyond the hippocampus. We primarily focus our efforts on the lateral septum; a region long implicated in social behaviors, densely innervated by the hippocampus and rich itself in OXTRs. In sum, we propose a research plan that distills oxytocin signaling in the hippocampus into its most elementary components: peptide release, receptor activation and cell-type specific modulation of the M-current. Then, as an acid test of our understanding, we attempt to reconstruct oxytocin’s modulatory actions using our newly developed optical tools. Finally, we consider how oxytocin signaling in the hippocampus may propagate to downstream structures, ultimately influencing social behavior.
项目总结(项目3,合作项目:Tsien, Froemke, Buzsaki)

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 }}

RICHARD W TSIEN其他文献

RICHARD W TSIEN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('RICHARD W TSIEN', 18)}}的其他基金

Oxytocin Modulation of Neural Circuit Function and Behavior
催产素对神经回路功能和行为的调节
  • 批准号:
    10676011
  • 财政年份:
    2022
  • 资助金额:
    $ 40.72万
  • 项目类别:
Calcium Channels, CaMKII and Mechanisms of Excitation-Transcription Coupling
钙通道、CaMKII 和兴奋转录偶联机制
  • 批准号:
    10522762
  • 财政年份:
    2022
  • 资助金额:
    $ 40.72万
  • 项目类别:
Calcium Channels, CaMKII and Mechanisms of Excitation-Transcription Coupling
钙通道、CaMKII 和兴奋转录偶联机制
  • 批准号:
    10636887
  • 财政年份:
    2022
  • 资助金额:
    $ 40.72万
  • 项目类别:
Oxytocin Modulation of Neural Circuit Function and Behavior
催产素对神经回路功能和行为的调节
  • 批准号:
    10220151
  • 财政年份:
    2018
  • 资助金额:
    $ 40.72万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10705991
  • 财政年份:
    2018
  • 资助金额:
    $ 40.72万
  • 项目类别:
Oxytocin Modulation of Neural Circuit Function and Behavior
催产素对神经回路功能和行为的调节
  • 批准号:
    10438587
  • 财政年份:
    2018
  • 资助金额:
    $ 40.72万
  • 项目类别:
Oxytocin Modulation of Neural Circuit Function and Behavior
催产素对神经回路功能和行为的调节
  • 批准号:
    10705986
  • 财政年份:
    2018
  • 资助金额:
    $ 40.72万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10678791
  • 财政年份:
    2018
  • 资助金额:
    $ 40.72万
  • 项目类别:
Oxytocin Modulation of Neural Circuit Function and Behavior - Revision - 3
催产素对神经回路功能和行为的调节 - 修订版 - 3
  • 批准号:
    10601831
  • 财政年份:
    2018
  • 资助金额:
    $ 40.72万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10220152
  • 财政年份:
    2018
  • 资助金额:
    $ 40.72万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 40.72万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了