Ancient gill and lung oscillators may generate the respiratory rhythm of frogs and rats

Abstract

Though the mechanics of breathing differ fundamentally between amniotes and "lower" vertebrates, homologous rhythm generators may drive air breathing in all lunged vertebrates. In both frogs and rats, two coupled oscillators, one active during the inspiratory (I) phase and the other active during the preinspiratory (PreI) phase, have been hypothesized to generate the respiratory rhythm. We used opioids to uncouple these oscillators. In the intact rat, complete arrest of the external rhythm by opioid-induced suppression of the putative I oscillator, that is, pre-Bötz-inger complex (PBC) oscillator, did not arrest the putative PreI oscillator. In the unanesthetized frog, the comparable PreI oscillator, that is, the putative buccal/ gill oscillator, was refractory to opioids even though the comparable I oscillator, the putative lung oscillator, was arrested. Studies in en bloc brainstem preparations derived from both juvenile frogs and metamorphic tadpoles confirmed these results and suggested that opioids may play a role in the clustering of lung bursts into episodes. As the frog and rat respiratory circuitry produce functionally equivalent motor outputs during lung inflation, these data argue for a close homology between the frog and rat oscillators. We suggest that the respiratory rhythm of all lunged vertebrates is generated by paired coupled oscillators. These may have originated from the gill and lung oscillators of the earliest air breathers.

Neural mechanisms underlying respiratory rhythm generation in the lamprey

“…In agreement with Kinkead (2009), we believe that the lamprey pTRG displays a high homology not only with the mammalian preBötC, but also with the neural mechanisms generating lung ventilation in amphibians (Wilson et al, 2002;Vasilakos et al, 2005;Chen and Hedrick, 2008;Kottick et al, 2013) and turtles (Johnson et al, 2002(Johnson et al, , 2007, rather than with those that generate gill respiration in tadpoles (Galante et al, 1996;Broch et al, 2002). All these different oscillators have as a possible underlying rhythm generating mechanism the "group-pacemaker" model (Del Negro et al, 2005;Feldman and Del Negro, 2006).…”

“…These latter, along with spinal motor nuclei innervating the intercostal muscles and diaphragm, progressively acquire a prominent respiratory role. These changes in the location of the respiratory CPG obviously imply a caudal migration of the original rhythm generating mechanism or the development of a new respiratory oscillator or multiple oscillators, entrained to a large degree (Wilson et al, 2002(Wilson et al, , 2006Vasilakos et al, 2005;Taylor et al, 2010;Kottick et al, 2013). The respiratory CPG of higher vertebrates and mammals remains placed in a cranial strategic position to drive close brainstem motoneurons that have to be engaged in advance and to send excitatory projections to lower respiratory muscles innervated by spinal motoneurons.…”

Breathing withPhox2b

“…Conversely, the preBö tC would be an invention of terrestrial vertebrates, possibly homologous to the 'lung oscillator' of amphibians. A cautionary note here is that the anatomical positions of the buccal and lung oscillators of frogs are not readily reconcilable with those of the pFRG and preBö tC, respectively (Vasilakos et al 2005). When we have a cellular definition of the respiratory oscillator(s) of fish or amphibians, testing for Phox2b expression might provide an argument for or against homology.…”

Chaotic dynamics of resting ventilatory flow in humans assessed through noise titration

“…A neural source for respiratory chaos is a likely hypothesis, because it is widely accepted that the central respiratory command depends on at least two coupled oscillators (see review in Feldman et al, 2003;Mellen et al, 2003; see also Vasilakos et al, 2005). Compound neural oscillator models of the mammalian respiratory rhythm can exhibit complex dynamical behaviors under various periodic inputs (Matsugu et al, 1998), and the study of breath-to-breath variations in tidal volume, end-tidal O 2 and end-tidal However, nonlinearities in the flow pattern could also be created, or altered, by the nature of the media to which the respiratory neural command is applied.…”