NETWORK INTERACTIONS IN RESPIRATORY NEURON POPULATIONS

描述（由申请人提供）：在去大脑大鼠中，该项目将研究脑干吸气神经元不同群体内和之间的短期相互作用，表现为高频振荡（HFO，100-150 Hz）。将从分离的神经元中进行细胞内和细胞外记录，并以膈神经输出作为参考信号，通过间隔、相关性和频谱分析来表征其活动中的快节律。 将进行脑干吸气神经元的调查，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。几个实验演习将应用于确定兴奋性和抑制性神经相互作用如何产生的节奏。 1)强迫振荡（共振）分析将用于确定各种放电频率模式在产生吸气（膈）输出方面的可能差异功效。这将通过将具有不同参数的刺激串递送到下行球脊髓轴突来完成。 2)通过在HFO节律的各个阶段传递传入输入（例如，上级喉或迷走神经刺激）来研究不同神经元群体之间的反馈相互作用的机制，以确定相位响应曲线并引发相位重置。 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电渗，并通过分析HFO模式的差异变化，研究不同兴奋性和抑制性递质作用对不同类型神经元中HFO的影响。 4)细胞内记录将用于通过注射去极化或超极化电流揭示兴奋性和抑制性HFO相关输入的类型。来自成对单元的同时记录（一个在细胞外记录，一个在细胞内记录）将揭示不同类型的HFO相关性。 意义HFO揭示的相互作用导致吸气阶段内放电模式的形成和成形，以及放电幅度的控制。运动神经元输入的节律性可能影响运动输出的效能，从而有助于对呼吸驱动变化的适应。在其他神经系统中出现的类似振荡表明存在普遍的网络相互作用模式。

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.