The role of pFRG neurons in the respiratory network.
pFRG 神经元在呼吸网络中的作用。
基本信息
- 批准号:7486442
- 负责人:
- 金额:$ 5.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-07-16 至 2010-07-15
- 项目状态:已结题
- 来源:
- 关键词:Adaptive BehaviorsAffectAutomobile DrivingBirthBlack raceBrain StemBreathingCell NucleusColorComplexCoupledDevelopmentDrug usageDyesFire - disastersGenerationsGoalsHourHumanIndividualKnockout MiceLifeLinkLocationMonitorMorphologyMotor ActivityMotor outputMusNervous system structureNeuronsPathologyPatternPharmaceutical PreparationsPlayPreparationPublic HealthRattusResearchRestRoleRunningSleep DisordersSliceSpeedSpinal CordSpinal nerve structureStagingStructureSystemTestingTherapeuticThickTransgenic MiceWorkdayexpirationimprovedneural circuitnovelpostnatalrelating to nervous systemresearch studyrespiratory
项目摘要
DESCRIPTION (provided by applicant): Breathing is a robust and adaptive behavior, and its complexity is often overlooked because of its constant presence. Recent work suggests that breathing is produced by two distinct rhythmic centers in the brainstem. One hypothesis is that each center is responsible for a specific aspect of breathing: one center is responsible for inspiration (preBotzinger complex, preBotC), the other is responsible for active expiration (parafacial respiratory group, pFRG). To date, the connectivity between these two centers is unclear as is the precise role of the pFRG. To begin to understand the interplay between the preBotC and the pFRG, we will characterize the direct and indirect anatomical connectivity between the two centers by injecting dyes of different colors into the different centers and performing tract-tracing experiments (AimlA). We will obtain electrical recordings from single neurons in each center and reconstruct their morphology (AimlB). We will thus gain a clearer picture of how the two centers are connected, including the identification of indirect connections in the medulla. For individual neurons in each center we will begin to link firing patterns to specific anatomical projections. Both sets of experiments will increase our understanding of the organization of the neural circuit for breathing. To determine the role of each rhythmic center in breathing, we will use drugs to selectively and reversibly speed up or slow down one rhythmic center (pFRG or preBotC) while continuously monitoring breathing-related motor activity on distinct spinal nerves (Aim2A). Using drugs, we will reversibly silence the pFRG and characterize changes in the breathing rhythm and pattern. Related to these experiments, we will provide further quantification of the breathing rhythm and pattern in transgenic mice (Krox20-/-) that have pFRG/RTN pathology (Aim2B). If our running hypothesis is correct, the mice without a functional pFRG should have breathing rhythms that are similar to those observed in rats where the pFRG is reversibly silenced. Last, we will optically monitor the breathing centers when one neuron is stimulated to look at within center and between center connectivity (Aim3). Public health relevance: ln humans, breathing is essential to life and requires that the nervous system generate a reliable and robust rhythm. The proposed study aims to understand how two rhythmic brainstem centers are connected and how they interact to produce breathing. This information can aid in the development of rational therapeutics for central sleep disorders and will improve our understanding of the neural systems that are involved in the breathing rhythm.
描述(由申请人提供):呼吸是一种稳健和适应性的行为,由于其持续存在,其复杂性往往被忽视。最近的研究表明,呼吸是由脑干中两个不同的节律中心产生的。一种假设是每个中心负责呼吸的特定方面:一个中心负责吸气(preBotzinger复合体,preBotC),另一个负责主动呼气(旁面呼吸组,pFRG)。迄今为止,这两个中心之间的连接尚不清楚,pFRG的确切作用也不清楚。为了开始理解preBotC和pFRG之间的相互作用,我们将通过将不同颜色的染料注射到不同的中心并进行追踪实验(AimlA)来表征两个中心之间的直接和间接解剖学连接。我们将从每个中心的单个神经元获得电记录并重建其形态(AimlB)。因此,我们将更清楚地了解这两个中心是如何连接的,包括识别髓质中的间接连接。对于每个中心的单个神经元,我们将开始将放电模式与特定的解剖投影联系起来。这两组实验将增加我们对呼吸神经回路组织的理解。为了确定每个节律中心在呼吸中的作用,我们将使用药物选择性地和可逆地加速或减慢一个节律中心(pFRG或preBotC),同时连续监测不同脊神经(Aim 2A)上与呼吸相关的运动活动。使用药物,我们将可逆地沉默pFRG,并描述呼吸节律和模式的变化。与这些实验相关,我们将提供具有pFRG/RTN病理(Aim 2B)的转基因小鼠(Krox 20-/-)中呼吸节律和模式的进一步定量。如果我们的跑步假设是正确的,那么没有功能性pFRG的小鼠的呼吸节律应该与pFRG可逆性沉默的大鼠相似。最后,当一个神经元被刺激以观察中心内和中心之间的连接时,我们将光学监测呼吸中心(Aim 3)。公共卫生相关性:在人类中,呼吸对生命至关重要,需要神经系统产生可靠和强大的节奏。这项研究的目的是了解两个有节奏的脑干中心是如何连接的,以及它们是如何相互作用产生呼吸的。这些信息可以帮助开发中枢性睡眠障碍的合理疗法,并将提高我们对呼吸节律所涉及的神经系统的理解。
项目成果
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Serapio Michael Baca其他文献
Serapio Michael Baca的其他文献
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{{ truncateString('Serapio Michael Baca', 18)}}的其他基金
The role of pFRG neurons in the respiratory network.
pFRG 神经元在呼吸网络中的作用。
- 批准号:
7665056 - 财政年份:2008
- 资助金额:
$ 5.13万 - 项目类别:
LEECH LOCAL BENDING: UNDERSTANDING A SENSORY MOTOR LOOP
水蛭局部弯曲:了解感觉运动回路
- 批准号:
6530833 - 财政年份:2002
- 资助金额:
$ 5.13万 - 项目类别:
LEECH LOCAL BENDING: UNDERSTANDING A SENSORY MOTOR LOOP
水蛭局部弯曲:了解感觉运动回路
- 批准号:
6637575 - 财政年份:2002
- 资助金额:
$ 5.13万 - 项目类别:
LEECH LOCAL BENDING: UNDERSTANDING A SENSORY MOTOR LOOP
水蛭局部弯曲:了解感觉运动回路
- 批准号:
6313383 - 财政年份:2001
- 资助金额:
$ 5.13万 - 项目类别:
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