Episodic breathing in frogs: Converging hypotheses on neural control of respiration in air breathing vertebrates

American Zoologist, Feb 1997 by Richard Kinkead

SYNOPSIS. The episodic, or intermittent, breathing of frogs and many ectothermic vertebrates results in important fluctuations of arterial blood gases. This pattern of breathing differs from the rhythmic and continuous alternation of inspiration observed in most homeotherms, which maintain 02 and COZ levels within narrow ranges. These differences in pattern of breathing indicate that the respiratory control systems of ectotherms and homeotherms differ substantially. The results of recent studies using in vitro brainstemspinal cord preparations of adult frogs and premetamorphic tadpoles (Rana catesbeiana and Rana pipiens) demonstrate, however, that the mechanisms for rhythm generation and pattern formation described previously for mammals are also key features of the respiratory control system of frogs. These findings therefore support the hypothesis that the respiratory control system is highly conserved amongst air breathing vertebrates, whether they breathe continuously or episodically.

Episodic Breathing in Frogs: Converging Hypotheses on Neural Control of Respiration in Air Breathing Vertebrates1

INTRODUCTION

The main roles of the respiratory control system are to drive and regulate convection of air or water over the gas exchange structure, and ultimately maintain arterial CO, and Oz levels relatively constant. For most mammals, the homeostasis of arterial blood gases results from rhythmic, uninterrupted alternation between inspiration and expiration. This breathing pattern contrasts with the one produced by many ectothermic vertebrates in which lung ventilation occurs in single events or is grouped into episodes of many breaths separated by non-ventilatory (apneic) periods of variable duration. These non-ventilatory pauses result in important fluctuations of arterial blood gases, but are not detrimental because ectotherms have lower metabolic rates than hometotherms and tolerate hypoxia and hypercapnia very well. Thus, gas exchange does not need to be continuous to meet metabolic demands. While episodic breathing is well suited to the life style of many ectotherms, such as frogs, turtles, and crocodilians which dive frequently, it also optimizes the cost of ventilation in some species (Vitalis and Milsom, 1986). The imprecise control of arterial blood gases of episodically breathing animals suggests, however, that the respiratory control system of these ectotherms differs from the one of mammals. It is indeed difficult to conceive that episodic breathing is produced by a central respiratory rhythm generator similar to that described in mammals (see below). It has been proposed, therefore, that amphibian ventilatory activity may be switched on and off by appropriate trigger signals arising from the changing conditions during apnea or breathing (Shelton and Boutilier, 1982; Shelton and Croghan, 1988). The control system is a feedback loop in which chemoreceptors are involved in detecting the error signal from arterial blood gases and the cerebrospinal fluid (CSF). In this scenario, the central nervous system (CNS) establishes the set-point(s) around which blood gas fluctuations are regulated.

The mammalian respiratory control system is hypothesized to consist of a rhythm generator that produces the underlying fundamental oscillation (i.e., frequency of breathing) and pattern forming neural circuitry that integrates a wide variety of sensory inputs to produce a complex spatiotemporal pattern of motor output to the respiratory muscles. Breathing then meets the convective requirements while also accommodating other activities (e.g., feeding, running, vocalizing) (Feldman et al., 1990). Because lung ventilation occurs intermittently in most ectotherms, no intrinsic rhythm is obvious. As a result, the concept of rhythm generation as a part of the respiratory control system in episodic breathers has not received much support. Yet in the bullfrog (Rana catesbeiana) the small amplitude, highly regular, buccal oscillations (described below) and the lung ventilations within a bout of ventilation are produced rhythmically, because the period between two successive, uninterrupted buccal oscillations or lung ventilations has little variability (Kinkead and Milsom, 1994, 1996). In addition, the potential for an underlying rhythm generator becomes obvious at high levels of respiratory drive when frogs breathe continuously.

In mammals, pattern is defined solely in terms of the time spent in inspiration (TI) and expiration (TE) and the rate of air flow. Combinations of these variables produce the more familiar components of breathing, namely, tidal volume (flow/TI), breathing frequency (60/TI TE), and minute ventilation (frequency X tidal volume). Pattern is more complex in episodic breathers where the components of breathing frequency also include the duration of the nonventilatory period and the number of breaths per episode. Thus, the respiratory control system of ectotherms conceivably resembles the mammalian control system; the rhythmogenic and pattern forming elements in each are adapted to meet the demands determined by the environment, behavior, metabolic needs, and breathing mechanics. Unfortunately, this hypothesis is hampered by our lack of understanding of the respiratory control system in ectothermic vertebrates (Shelton et al., 1986).