NETWORK INTERACTIONS IN RESPIRATORY NEURON POPULATIONS

描述(申请人提供)：在去大脑的大鼠中，该项目将研究不同群体脑干吸气神经元内部和之间的短期相互作用，表现为高频振荡(HFO，100-150赫兹)。细胞内和细胞外的记录将从分离的神经元中获得，其活动的快速节律将以膈神经输出为参考信号，通过间隔、相关和频谱分析来表征。 将对脑干吸气神经元进行调查，以表征它们的HFO特性、放电模式、解剖位置和投射之间的关系。几个实验动作将被用来确定兴奋性和抑制性神经相互作用如何产生节律。 1)强迫振荡(共振)分析将被用来确定不同放电频率模式在产生吸气(膈)输出方面可能的不同效果。这将通过向球脊髓下行轴突输送具有不同参数的刺激列车来实现。 2)通过在HFO节律的不同阶段传递传入信息(例如，喉上或迷走神经刺激)来研究不同神经元群体之间反馈相互作用的机制，以确定阶段反应曲线并引发阶段重置。 3)通过对单个细胞外记录的脑干神经元进行激动剂和拮抗剂的离子导入，以及通过分析HFO模式的差异变化，来研究不同类型神经元中不同的兴奋和抑制递质作用对HFO的影响。 4)细胞内记录将通过注入去极化或超极化电流来揭示兴奋性和抑制性HFO相关输入的类型。成对单位的同时记录(一个细胞外记录和一个细胞内记录)将显示不同类型的与HFO相关的相关性。 意义重大。HFO揭示的相互作用导致吸气相内放电模式的形成和塑造，以及对放电幅度的控制。运动神经元输入的节律性可能会影响运动输出的效果，从而帮助适应呼吸驱动的变化。在其他神经系统中出现类似的振荡现象表明网络相互作用的普遍模式的存在。

DESCRIPTION (provided by applicant): In the decerebrate rat, the project will study the short-term interactions, manifested in high-frequency; oscillations (HFOs, 100-150 Hz), within and between different populations of brainstem inspiratory neurons. Intracellular and extracellular recordings will be taken from isolated neurons, and the fast rhythms in their activities will be characterized by interval, correlation, and spectral analysis with phrenic nerve output as the reference signal. A survey of brainstem inspiratory neurons will be conducted, to characterize relations between their HFO properties, firing patterns, anatomical locations, and projections. Several experimental maneuvers will be applied to ascertain how excitatory and inhibitory neural interactions generate the rhythm. 1) Forcing oscillation (resonance) analysis will be used to ascertain the possible differential efficacy of various discharge frequency patterns in producing inspiratory (phrenic) output. This will be done by delivery of stimulus trains having different parameters to descending bulbospinal axons. 2) The mechanisms of feedback interactions between different neuron populations will be studied by delivery of afferent inputs (e.g, superior laryngeal or vagal stimulation) at various phases of the HFO rhythm to determine phase response curves and to elicit phase resetting. 3) The effects of different excitatory and inhibitory transmitter actions on HFOs in different types of neurons will be studied by iontophoresis of agonists and antagonists on individual extracellularly recorded brainstem neurons and by analysis of differential changes of HFO pattern. 4) Intracellular recordings will be used to reveal types of excitatory and inhibitory HFO-related inputs by injection of depolarizing or hyperpolarizing current. Simultaneous recordings from pairs of units (one extracellularly and one intracellularly recorded) will reveal different types of HFO-related correlation. Significance. The interactions revealed by HFOs result in the formation and shaping of discharge patterns within the inspiratory phase, as well as in the control of amplitude of discharge. The rhythmicity of inputs to motoneurons may influence the efficacy of motor output and thus help adaptation to changes of respiratory drive. The occurrence of similar oscillations in other neural systems suggests the existence of universal modes of network interaction.