BRAINSTEM RESPIRATORY NEURON INTERACTIONS

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The goal of this research is to define the functional organization and internal operations of the brainstem neural network through which carotid baroreceptors and chemoreceptors regulate breathing. Carotid chemoreceptors and baroreceptors will be selectively stimulated to perturb respiratory related neural activity in anesthetized or decerebrate artificially ventilated cats. Spike train analysis methods (e.g., gravity, joint peristimulus time histograms), optical measurements of scattered light signals, and spike triggered averaging of intracellular recordings, will be used to assess dynamic functional connectivity among cardiorespiratory related neurons. The plausibility of network models derived from these approaches will be tested with computer simulations. Planned experiments will address six hypotheses. 1. Long-term facilitation (LTF) of respiratory drive induced by carotid chemoreceptor stimulation can be "erased" in a graded manner by carotid baroreceptor stimulation. Removal of LTF resets the equilibrium state of a distributed neuronal assembly that regulates the gain of these reflexes and respiratory drive. 2. Interactions among neurons of the nucleus tractus solitarius (NTS) that respond to carotid baroreceptors or chemoreceptors contribute to dynamic gain control of inputs from these receptors. 3. Neurons in the caudal NTS carry information from carotid chemoreceptors and baroreceptors to cardiorespiratory raphe neurons. 4. Raphe neuronal assemblies influence the responsiveness of NTS neurons to carotid baroreceptors and chemoreceptors through the dynamic modulation of impulse synchrony among NTS neurons. 5. Raphe neurons influence breathing and vasomotor reflexes through common "multifunctional" interneurons in the caudal and rostral ventrolateral medulla. 6. Synchronous assemblies of raphe neurons converge on premotor bulbospinal neurons. Long-term facilitation of respiratory drive is due, at least in part, to maintained changes in firing rate of raphe neurons that innervate these neurons. Numerous disorders of breathing and cardiovascular control result from abnormalities in the central nervous system. Improved treatments and management of these problems are dependent on a better understanding of the neural networks that regulate these functions.