The control of episodic breathing in the bullfrog (Rana catesbeiana)

Like many lower vertebrates, bullfrogs breathe episodically; i.e. breathing occurs in bouts that are interrupted by periods of apnea. This breathing pattern contrasts with the continuous alternation between inspiration and expiration usually seen in mammals. Little is known about the mechanisms underlying episodic breathing; hence, the objective of this thesis was to investigate respiratory control in the bullfrog to determine what causes the onset/termination of the episodes of breathing. A variety of preparations, ranging from the “ta (whole) animal to the in vitro brainstem-spinal cord preparation were used. This reductionist approach made it possible to assess the contribution of the different components of the respiratory control system towards pattern formation. The initial studies focused on the role of afferent feedback from different groups of peripheral receptors. In these experiments, receptor input was either eliminated by denervation or manipulated artificially. The results have shown that each receptor group influences pattern differently, either by affecting the number of breaths in an episode, or the duration of the apneic (non-ventilatory) period. However, none of the receptor groups investigated were responsible for clustering the breaths into episodes. These results were subsequently confirmed by recording the respiratory-related motor output from an in vitro brainstem-spinal cord preparation, which produced a “fictive” breathing pattern that was episodic, and virtually identical to that of intact frogs. Because this preparation is essentially devoid of afferent feedback (except for central chemoreceptors) and descending inputs but still can produce breathing episodes, it was concluded that the episodic breathing pattern of the bullfrog is an intrinsic property of the central nervous system, and can occur without peripheral feedback. The final study assessed the role of the nucleus isthmi in breathing pattern formation. This nucleus is located between the midbrain roof and the base of the cerebellum. Bilateral microinjections of the neurotoxin kainic acid in the nucleus isthmi area significantly reduced the breathing frequency, and the breathing pattern consisted mainly of evenly-spaced single breaths. This suggests that the nucleus isthmi provides the tonic drive to breathe, which is a key element in the production of breathing episodes of more than one breath. It is concluded that the mechanisms accounting for the onset/termination of breathing episodes may reflect a property of the neuronal circuitry responsible for respiratory rhythmogenesis, and/or burst pattern formation rather than an interaction between afferent inputs and the central nervous system.Science, Faculty ofZoology, Department ofGraduat