NETWORK INTERACTIONS IN RESPIRATORY NEURON POPULATIONS

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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.