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
- 来源:
- 关键词:AcuteAdvisory CommitteesAnimalsAwardBehavioralBindingBlood gasBrainBrain StemBreathingCharacteristicsChronicCompensationComplementComplexContractsDataDiseaseElectrophysiology (science)EnsureEquilibriumExhibitsFeedbackFundingGenerationsGeneticGoalsHealthHomeostasisImageImmunoprecipitationIn VitroInstitutionInterneuronsK-Series Research Career ProgramsLifeMembraneMentorsMentorshipMetabolicMolecularMotorMusNeuronsOrganismPathologyPeriodicalsPeriodicityPharmacologyPhasePositioning AttributePreparationPropertyProteinsRecurrenceRegulationResearchRespiration DisordersRespiratory FailureRespiratory physiologyRoleSliceSynapsesTechniquesTestingTrainingTransfectionViralWorkcareercareer developmentcentral pattern generatorexcitatory neuronexperienceexperimental studygenetic approachin vivoinhibitory neuronnervous system disorderneural networknoveloptogeneticspH HomeostasispharmacologicpostsynapticpreBotzinger complexprofessorprogramsresearch and developmentrespiratoryresponsesynaptic inhibitionventilation
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.
项目总结
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。
- DOI:10.1101/2023.10.30.564834
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Phillips,RyanS;Baertsch,NathanA
- 通讯作者:Baertsch,NathanA
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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