Search

During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO 2 pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over a century of investigation. In the past three decades, neuroscience has advanced tremendously, raising optimism that the 'exercise hyperpnoea dilemma' can finally be solved. In this review, new perspectives are offered in the hope of stimulating original ideas based on modern neuroscience methods and current understanding. We first describe the ventilatory control system and the challenge exercise places upon blood-gas regulation. We highlight relevant system properties, including feedforward, feedback and adaptive (i.e., plasticity) control of breathing. We then elaborate a seldom explored hypothesis that the exercise ventilatory response continuously adapts (learns and relearns) throughout life and ponder if the memory 'engram' encoding the feedforward exercise ventilatory stimulus could reside within the cerebellum. Our hypotheses are based on accumulating evidence supporting the cerebellum's role in motor learning and the numerous direct and indirect projections from deep cerebellar nuclei to brainstem respiratory neurons. We propose that cerebellar learning may be obligatory for the accurate and adjustable exercise hyperpnoea capable of tracking changes in life conditions/experiences, and that learning arises from specific cerebellar microcircuits that can be interrogated using powerful techniques such as optogenetics and chemogenetics. Although this review is speculative, we consider it essential to reframe our perspective if we are to solve the till-now intractable exercise hyperpnoea dilemma., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the central question of this study? This study is the first to measure objectively both inspiratory and expiratory muscle fatigue after inspiratory resistive loading to determine whether the expiratory muscles are activated to the point of fatigue when specifically loading the inspiratory muscles. What is the main finding and its importance? The absence of abdominal muscle fatigue suggests that future studies attempting to understand the neural and circulatory consequences of diaphragm fatigue can use inspiratory resistive loading without considering the confounding effects of abdominal muscle fatigue. Expiratory resistive loading elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel coactivation of the inspiratory muscles during expiration. It is unknown whether the expiratory muscles are likewise coactivated to the point of fatigue during inspiratory resistive loading (IRL). The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Healthy male subjects (n = 9) underwent isocapnic IRL (60% maximal inspiratory pressure, 15 breaths min -1 , 0.7 inspiratory duty cycle) to task failure. Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (P ga,tw ) and transdiaphragmatic twitch pressure (P di,tw ) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Fatigue was defined as a significant reduction from baseline in P ga,tw or P di,tw . Throughout IRL, there was a time-dependent increase in cardiac frequency and mean arterial blood pressure, suggesting activation of the respiratory muscle metaboreflex. The P di,tw was significantly lower than baseline (34.3 ± 9.6 cmH 2 O) at 3 (23.2 ± 5.7 cmH 2 O, P < 0.001), 15 (24.2 ± 5.1 cmH 2 O, P < 0.001) and 30 min post-IRL (26.3 ± 6.0 cmH 2 O, P < 0.001). The P ga,tw was not significantly different from baseline (37.6 ± 17.1 cmH 2 O) at 3 (36.5 ± 14.6 cmH 2 O), 15 (33.7 ± 12.4 cmH 2 O) and 30 min post-IRL (32.9 ± 11.3 cmH 2 O). Inspiratory resistive loading elicits objective evidence of diaphragm, but not abdominal, muscle fatigue. Agonist-antagonist interactions for the respiratory muscles appear to be more important during expiratory versus inspiratory loading., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)