Homeostatic Plasticity of the Respiratory Rhythm Generating Network

呼吸节律生成网络的稳态可塑性

基本信息

  • 批准号:
    10615743
  • 负责人:
  • 金额:
    $ 24.9万
  • 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:
    2021-05-01 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY This career development award will allow the Candidate, Dr. Nathan Baertsch, to establish an independent research career focused on unravelling how the brain adapts to maintain breathing during disease. The training plan outlined in this award combined with the Candidate’s background in motor plasticity, respiratory physiology and rhythm generation make him ideally suited to successfully follow this career development path. The breathing rhythm is generated by periodic synchronization of excitatory interneurons in the preBötzinger Complex (preBötC). The search for the essential rhythmogenic mechanism has been a central question in the control of breathing field for over two decades. Although this search has revealed many important discoveries, it has overlooked perhaps one of the most fundamental characteristics of the network – its ability to adapt. The amount of synchronization among preBötC neurons is not fixed, but depends on a dynamic interplay between excitatory and inhibitory connections, and the intrinsic membrane properties of preBötC neurons. How this life- sustaining neural network regulates this precise balance of synaptic and intrinsic properties to ensure breathing remains robust is not well understood. Based on preliminary data, we hypothesize that the distribution of the network generating inspiration is adaptable, and the balance between synaptic excitation, inhibition, and intrinsic bursting properties can be homeostatically tuned to compensate for chronic perturbations that threaten rhythmogenesis and breathing. This project will build on the candidate’s prior training in electrophysiology, pharmacology, and optogenetics by introducing state-of-the-art chemogenetic, imaging, and molecular techniques. Combining these strategies will allow the Candidate to use a multi-level approach to characterize changes in the distribution of inspiratory activity (Aim1) and identify changes in synaptic and intrinsic properties (Aim2) in the preBötC following chronic disruptions in neuronal activity. These in vitro experiments using a novel brainstem slice preparation will be complemented with in vivo experiments to explore how breathing adapts to chronic suppression of preBötC activity in the intact animal (Aim3). To help the Candidate achieve the research and career development goals of this proposal, he will receive strong mentorship from Dr. Nino Ramirez, a leader in respiratory rhythm generation with a successful mentoring track- record. The Candidate will also receive research and career development support from an advisory committee of established professors and former K-awardees that have transitioned to independence. These PIs all work closely with the Candidate and are experts in the chemogenetic, imaging, and molecular techniques that will be training components of this proposal. With full institutional support and the additional training, mentorship, and experience that this K-award will provide, the Candidate will be well positioned to successfully compete for R01-funding and establish an impactful independent research program.
项目摘要 这个职业发展奖将允许候选人,博士内森Baertsch,建立一个独立的 他的研究生涯集中在揭示大脑如何适应疾病期间保持呼吸。的 该奖项中概述的培训计划结合候选人在运动可塑性,呼吸, 生理学和节奏生成使他非常适合成功地遵循这一职业发展道路。 呼吸节律是由前Bötzinger区兴奋性中间神经元的周期性同步产生的 Complex(preBötC).寻找基本的节律发生机制一直是研究的中心问题。 控制呼吸场超过二十年。虽然这次搜索揭示了许多重要的发现, 它忽略了网络的一个最基本的特征--适应能力。的 preBötC神经元之间的同步量不是固定的,而是取决于它们之间的动态相互作用。 兴奋性和抑制性连接,以及preBötC神经元的内在膜特性。怎么会这样- 维持神经网络调节突触和内在属性的精确平衡,以确保 呼吸保持强健还不是很清楚。根据初步数据,我们假设 产生灵感的网络的分布是自适应的,并且突触兴奋, 抑制和内在的爆发特性可以被稳态调节以补偿慢性的 威胁节奏发生和呼吸的扰动。这个项目将建立在候选人的事先 通过引入最先进的化学遗传学, 成像和分子技术。结合这些策略将允许候选人使用多层次 描述吸气活动(Aim 1)分布变化的方法,并确定 突触和内在特性(Aim 2)在preBötC神经元活动的慢性中断后。这些 使用新型脑干切片制备物的体外实验将与体内实验相补充, 探索呼吸如何适应完整动物中preBötC活性的慢性抑制(Aim 3)。帮助 候选人实现本建议书的研究和职业发展目标,他将获得强有力的 来自Nino Ramirez博士的指导,他是呼吸节律生成领域的领导者,拥有成功的指导轨迹- 记录候选人还将获得咨询委员会的研究和职业发展支持 已经过渡到独立的知名教授和前K奖获得者。这些PI都能工作 他们与候选人关系密切,是化学遗传学、成像和分子技术方面的专家, 本建议的培训内容。有了充分的机构支持和额外的培训,指导, 这一K奖将提供的经验,候选人将处于有利地位,成功竞争 R 01-资助并建立一个有影响力的独立研究计划。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons.
  • DOI:
    10.7554/elife.59799
  • 发表时间:
    2020-08-28
  • 期刊:
  • 影响因子:
    7.7
  • 作者:
    Bowen AJ;Chen JY;Huang YW;Baertsch NA;Park S;Palmiter RD
  • 通讯作者:
    Palmiter RD
Modeling breathing rhythms.
模拟呼吸节律。
  • DOI:
    10.7554/elife.46033
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    7.7
  • 作者:
    Ramirez,Jan-Marino;Baertsch,NathanA
  • 通讯作者:
    Baertsch,NathanA
Interdependence of cellular and network properties in respiratory rhythmogenesis.
呼吸节律发生中细胞和网络特性的相互依赖性。
Parabrachial tachykinin1-expressing neurons involved in state-dependent breathing control.
  • DOI:
    10.1038/s41467-023-36603-z
  • 发表时间:
    2023-02-21
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Arthurs, Joseph W.;Bowen, Anna J.;Palmiter, Richard D.;Baertsch, Nathan A.
  • 通讯作者:
    Baertsch, Nathan A.
How neural networks walk and chew gum.
神经网络如何行走和嚼口香糖。
  • DOI:
    10.1113/jp286287
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Baertsch,NathanA;Phillips,RyanS
  • 通讯作者:
    Phillips,RyanS
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Nathan Andrew Baertsch其他文献

Nathan Andrew Baertsch的其他文献

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{{ truncateString('Nathan Andrew Baertsch', 18)}}的其他基金

Unraveling a parabrachial circuit for the state-dependent control of rapid breathing
解开臂旁回路以实现快速呼吸的状态依赖控制
  • 批准号:
    10564191
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
Homeostatic Plasticity of the Respiratory Rhythm Generating Network
呼吸节律生成网络的稳态可塑性
  • 批准号:
    10362776
  • 财政年份:
    2021
  • 资助金额:
    $ 24.9万
  • 项目类别:
Homeostatic Plasticity of the Respiratory Rhythm Generating Network
呼吸节律生成网络的稳态可塑性
  • 批准号:
    10392515
  • 财政年份:
    2021
  • 资助金额:
    $ 24.9万
  • 项目类别:
The role of Dbx1-derived medullary neurons for rhythm generation in the intact respiratory network
Dbx1 衍生的髓质神经元在完整呼吸网络中节律生成中的作用
  • 批准号:
    9390708
  • 财政年份:
    2016
  • 资助金额:
    $ 24.9万
  • 项目类别:
The role of Dbx1-derived medullary neurons for rhythm generation in the intact respiratory network
Dbx1 衍生的髓质神经元在完整呼吸网络中节律生成中的作用
  • 批准号:
    9352686
  • 财政年份:
    2016
  • 资助金额:
    $ 24.9万
  • 项目类别:
The role of Dbx1-derived medullary neurons for rhythm generation in the intact respiratory network
Dbx1 衍生的髓质神经元在完整呼吸网络中节律生成中的作用
  • 批准号:
    9190066
  • 财政年份:
    2016
  • 资助金额:
    $ 24.9万
  • 项目类别:

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