Drowning a frog respiratory oscillator in a wash of network excitability

Abstract

To be part of a respiratory rhythm generating circuit, a brainstem nuclei must (1) have phasic activity timed to the rhythm (correlation), (2) be able to speed the rhythm when excited (sufficiency), and (3) be able to slow the rhythm or terminate it when inhibited (necessity). A discrete brainstem nucleus passing these tests is currently considered a critical site for respiratory rhythm generation (an oscillator) if the nuclei continues to be rhythmic when physically isolated.Compelling and accumulating evidence in support of oscillators has been found in many vertebrates including lampreys, bullfrogs, turtles, birds, mice and rats. In bullfrogs and rodents, three putative oscillators have been discovered: the lung power stroke, lung priming and buccal oscillators in frogs; and in mammals the para Facial Respiratory Group (pFRG), Post‐Inspiratory Complex (PICO), and the PreBötzinger Complex (PreBötC). As the buccal oscillator in frogs and the PreBötC in mammals are located in the same brainstem rhombomere, r7, they may be homologous. Identification of multiple ‐‐ possibly homomogous ‐‐ oscillators in different species has led to the Oscillator Hypothesis which, in its strongest form, posits that respiratory rhythm is produced solely by brainstem oscillators and phase of motor bursts is determine by their interaction.However, almost complete (90%) destruction of the putative PreBötC in goats over several days was insufficient to terminate breathing. One explanations for this observation is a network architecture in which respiratory oscillators are no more than isolatable units in a much larger rhythmogenic network. To test if this is the case in frogs, we (a) located the frog buccal oscillator using necessity and sufficiency tests in an isolated hemisected brainstem preparation; (b) increased the excitability of the hemisection which increases the frequency and amplitude of the buccal motor pattern; and (c) again tested for necessity. We found that with network excitation, the necessity of the buccal oscillator disappeared, replaced by distributed rhythmogenesis in the surrounding premotor network.These data suggest that the Oscillator Hypothesis may need to be revised in frogs and possibly other vertebrates; the existence of the buccal oscillator as a discrete site of rhythm generation appears to be state dependent and may only be demonstrable in some conditions.Support or Funding InformationThis work was supported by NSERCThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.