Timing Of Respiratory Motor Activity

During inspiration, firing rates increase monotonically in both inspiratory propriobulbar and bulbospinal neurons. Early in expiration, inspiratory propriobulbar neurons are silenced, but the activity of inspiratory bulbospinal neurons stops only momentarily, reappearing after a brief period of silence and then gradually declining as expiration proceeds. This PIIA corresponds in time to the period of firing of early-expiratory neurons in the DRG and VRG. Expiratory bulbospinal neurons are silent during this early phase of expiration, whereas inspiratory propriobulbar neurons are actively inhibited. Furthermore, because the time course of inhibition of the respiratory propriobulbar neurons is similar to the time course of activity of the early-expiratory units, it has been suggested that the respiratory rhythm is caused by inhibition of an inspiratory ramp generator by these early-expiratory neurons.
Based on these observations, it has been proposed that expiration be divided into two phases, EI and EII. The EI phase corresponds to the period of PIIA, whereas the EII phase corresponds to the period in which PIIA is absent and expiratory neuronal activity may be present. In some situations, PIIA may extend throughout expiration, suggesting that the respiratory rhythm does not depend on the occurrence of activity in expiratory neurons.
PIIA appears to be associated with “braking” of expiratory air flow by contraction of the inspiratory muscles. Increases in PIIA and prolongations in EI occur, for example, when the larynx is bypassed so as to decrease upper airway resistance. PIIA (EI) is markedly reduced or eliminated by vagotomy, suggesting that mechanoreceptors that sense lung volume and/or tracheal air flow are important inputs. Hypercapnia decreases the duration of EI, whereas hypoxia appears to do the reverse. Increases in PIIA may contribute to the increase in functional residual capacity (FRC) observed during hypoxia.
Respiratory timing can be significantly affected by the rostral pontine pneumotaxic center, which comprises the NPBM and KFN. This structure contains a number of neurons that have different patterns of firing: inspiratory, expiratory, or phase-spanning. When the vagi are intact, discharge patterns in the NPBM are mainly tonic, but they become more clearly phasic after vagotomy. Both the VRG and the DRG send projections to the pneumotaxic center, so that the respiratory activity seen in this center appears to be of medullary origin. Depending on the region involved, stimulation of the pneumotaxic center can either terminate or prolong inspiration. Stimulation of the dorsolateral region terminates inspiration. The earlier in inspiration the stimulation is applied, the stronger is the stimulus needed. If the pneumotaxic center is lesioned and the vagi are cut, an apneustic breathing pattern develops in anesthetized animals that is characterized by prolonged inspiratory time. If time is allowed for recovery, however, and the animal regains consciousness, breathing loses its apneustic quality. If the animal is then given anesthesia or allowed to go to sleep, the apneustic pattern returns. These observations suggest the lack of importance of the pneumotaxic center in generating the respiratory pattern, and indicate that an interaction between states of alertness and the activity of higher brain centers and the brain stem bulbopontine respiratory neurons can significantly affect respiratory rhythm.
It is not clear whether some or any of the different respiratory neurons described in fact make up the central pattern generator. Three different ways in which the central respiratory pattern may be produced in the brain have been proposed. In one, the pattern generator is composed only of inspiratory neurons; an inspiratory ramp continues until it is terminated by the activity of off-switch neurons. The off-switch neurons are triggered after some predetermined time or after the inspiratory ramp reaches some threshold level of activity. Both trigger and ramp neurons could be stimulated by hypoxia and hypercapnia. In this scheme, inspiration is a self-terminating process carried out by cells whose activity is confined to inspiration.
In a second hypothesis, the central pattern generator may include both inspiratory and expiratory cells affected by chemical drives causing tonic increases in the activity of each. The increasing ramplike discharge seen in inspiratory intercostal and phrenic nerves may result from a gradual decline in inhibition rather than a gradual increase in excitation. This hypothesis is based on the observation that during apnea induced by hypocapnia, decreases in PO2 elicit inspiratory tonic activity. Progressive decreases in PO2 during apnea elicit progressive increases in tonic inspiratory activity until at a critical level of hypoxia the respiratory rhythm reappears. On the other hand, hypocapnia under hyperoxic conditions produces continuous firing of expiratory neurons, which increases as PCO2 rises until rhythmic breathing resumes. This suggests hypoxia exerts an excitatory effect predominantly on inspiratory activity, and that hypercapnia affects expiratory motor activity.
The third idea is that respiratory rhythmogenesis arises in the antagonistic activity of inspiratory and early-expiratory neurons and does not depend on the activity of conventional expiratory neurons that peaks late in the expiratory phase.