The isolated neonate rat brainstem/spinal cord preparation will be used to investigate the interaction between neural populations mediating the generation of respiratory rhythm and afferent inputs that reset this rhythm. In this preparation, networks generating respiratory rhythm are fully functional, and their cellular and synaptic properties are readily accessible. Endogenous bursters (cells whose membrane potentials oscillate in the absence of synaptic input) have been identified in this preparation. In some models of respiratory rhythmogenesis, endogenous bursters determine respiratory frequency by their bursting frequency, which is known to be a function of their resting membrane potentials. Preliminary studies show that respiratory rhythm is reset by electrical stimulation to the vagus nerve in this preparation. The effect of stimulation is a function of when it occurs in the respiratory cycle: inspiration is shortened when the stimulus is applied during inspiration, expiration is lengthened when the stimulus is applied early in expiration, and shortened when the stimulus is applied late in expiration. If endogenous bursters determine respiratory frequency, then stimulus-induced resetting of respiratory rhythm must converge on these cells. Monitoring endogenous bursters during stimulus-induced resetting of respiratory rhythm will test this hypothesis, and differentiate between alternative models of the functional circuitry for respiratory rhythmogenesis. Characterizing the cellular and synaptic mechanisms mediating the interaction of centrally generated rhythm and afferent feedback may shed light on the neural basis of respiratory pathologies which arise out of the inappropriate coupling of centrally generated rhythm and sensory feedback. In this preparation the neural basis for such pathologies can be investigated, and novel therapeutic interventions developed.
