Neural Control Of Breathing Research Articles

Novel Data Supporting the Two Respiratory Rhythm Oscillator Hypothesis. Focus on “Respiration-Related Rhythmic Activity in the Rostral Medulla of Newborn Rats”

Among the most rewarding moments in scientific discovery are when the pieces of a puzzle provided by different laboratories start to fall into place, forming a coherent and new view of the world. Several years ago, a consensus was emerging that respiratory rhythm in mammals arose from a single

Neural Control of Breathing

Neural Control of Breathing

Sex steroid hormones and the neural control of breathing.

We review evidence that sex steroid hormones including estrogen, progesterone and testosterone are involved in the central neural control of breathing. Sex hormones may exert their effects on respiratory motoneurons via neuromodulators, in particular, the serotonergic system. Recent studies have shown that levels of serotonin (5HT) in the hypoglossal and phrenic nuclei are greater in female than in male rats. Serotonin-dependent plasticity in hypoglossal and phrenic motor output also differs in male and female rats. Changing levels of gonadal hormones throughout the estrus cycle coincide with changing levels of 5HT in respiratory motor nuclei, and gonadectomy in male rats results in a decrease in 5HT-dependent plasticity in respiratory motor output. We speculate that sex steroid hormones are critically involved in adaptations in the neural control of breathing throughout life, and that decreasing levels of these hormones with increasing age may have a negative influence on the respiratory control system in response to challenge.

The role of calcium-activated potassium channels in respiratory control.

The introduction of pharmacological and genetic tools has helped to understand the functional role of specific ion channel subtypes in the neural control of breathing. This review outlines the role one family of potassium channels, those, which are regulated by intracellular calcium. Calcium-activated potassium channels (K(+)ca) play important roles in determining the duration of single action potentials and in the frequency of action potentials in excitable cells. They have been classified based on their unitary conductances combined with their inhibition by a variety of pharmacologic substances. In this review the role of K(+)ca channels in respiratory control is outlined. The predictions of their contributions from modeling the respiratory system and the results of experiments in which they are individually blocked are discussed. Recently mice have been generated in which the expression of a single member of the K(+)ca channel family can be conditionally regulated. The repression of this small-conductance K(+)ca channel (SK3) as well as its overexpression affect baseline respiratory rhythm and the ventilatory response to hypoxia.

Respiratory activity in the facial nucleus in an in vitro brainstem of tadpole, Rana catesbeiana.

1. In studies of the central neural control of breathing, little advantage has been taken of comparative approaches. We have developed an in vitro brainstem preparation using larval Rana catesbeiana which generates two rhythmic neural activities characteristic of lung and gill ventilation. Based on the pattern of the facial (VII) nerve activity both lung and gill rhythm-related respiratory cycles were divided into three distinct phases. The purpose of this study was to characterize and classify membrane potential trajectories of respiratory motoneurons in the VII nucleus at intermediate stages (XII-XVII) of development. 2. Seventy-five respiratory-modulated neurons were recorded intracellularly within the facial motor nucleus region. Their resting membrane potential was between -40 and -80 mV. Sixty of them were identified as VII motoneurons and fifteen were non-antidromically activated. Membrane potentials of fifty-six of the seventy-five neurons were modulated with both lung (5-27 mV) and gill rhythms (3-15 mV) and the remaining nineteen neurons had only a modulation with lung rhythmicity (6-23 mV). No cells with gill modulation alone were observed. 3. All of the cells modulated with lung rhythmicity had only phase-bound depolarizing or hyperpolarizing membrane potential swings which could be categorized into four distinct patterns. In contrast, of the fifty-six cells modulated with gill rhythmicity, thirty-two were phasically depolarized during distinct phases of the gill cycle (four patterns were distinguished), whereas the remaining twenty-four were phase spanning with two distinct patterns. The magnitudes of lung and gill modulations were proportionally related to each other in the cells modulated with both rhythms. 4. In all sixteen neurons studied, a reduction or a reversal of phasic inhibitory inputs during a portion of the lung or gill respiratory cycle was observed following a negative current or chloride ion (Cl-) injection. The phasic membrane resistance modulation in relation to the gill rhythm was analysed in six neurons and a relative decrease in the somatic membrane resistance (0.7-8.1 M omega) was detected during the periods of hyperpolarization. 5. We propose that, at these intermediate stages of development: (a) both gill and lung respiratory oscillations in motoneurons are generated by respiratory premotor neurons having only a few distinct activity patterns; (b) these patterns delineate distinct portions of the centrally generated respiratory cycles; and (c) phasic synaptic inhibition, mediated by Cl-, contributes to shaping the membrane potential trajectories of respiratory motoneurons.

Phrenic responses to contralateral spinal stimulation in rats: effects of old age or chronic spinal hemisection

Serotonin reveals ineffective spinal pathways from the C2-lateral funiculus to contralateral phrenic motoneurons in young adult rats with acute spinal hemisection. We tested the hypothesis that old age (1.5–2 years) or chronic hemisection (3–5 days) strengthens these pre-existing crossed spinal pathways. There were no consistent differences between young adult rats with acute hemisection versus young adult rats with chronic hemisection or old rat with acute hemisection except that one long-latency phrenic excitation could not be elicited in old rats. The results indicate that neither old age nor chronic hemisection strengthens crossed-spinal pathways, but that old age may selectively diminish spinal pathways involved in the neural control of breathing.

Respiratory responses induced by the activation of somatic nociceptive afferents in humans

To further investigate the role of somatic nociceptive afferents in the neural control of breathing, we studied the respiratory effects of their activation by means of either electrical stimulation or ischemic pain in 14 healthy volunteers. Painful electrical cutaneous stimulation increased respiratory frequency (f), mean inspiratory flow (VT/TI), and rate of rise (XP/TI) of integrated electromyographic activity of diaphragm (IEMGdi). Painful muscular electrical stimulation caused similar but larger changes accompanied by increases in tidal volume (VT), peak XP of IEMGdi, and ventilation (VE); it also entrained respiratory rhythm. Ischemic pain, which was characterized by a progressively increasing intensity, caused augmentation in respiratory activity that displayed an increasing trend: VE, f, VT, XP, VT/TI, and XP/TI increased. In the light of available literature, it seems conceivable to suggest that respiratory responses to painful electrical stimulation are mediated through the activation of cutaneous (A delta) and muscular (group III) fine-myelinated afferents, and responses to ischemic pain are mediated by the activation of both fine myelinated (group III) and unmyelinated (group IV) muscular afferents. The input conveyed by these afferents may constitute an effective stimulus to respiration in humans.

Recovery of breathing pattern after 15 min of cerebral ischemia in rabbits

The study was undertaken to ascertain the neural control of breathing and vagal reflexes during and after cerebral ischemia. The experiments were performed on anesthetized, paralyzed, and artificially ventilated rabbits. Cerebral ischemia was induced by reversible intrathoracic occlusion of the brachiocephalic trunk and the left subclavian and both internal thoracic arteries for 15 min. The effect of cerebral ischemia on breathing pattern was assessed by monitoring the integrated activities of phrenic and recurrent laryngeal nerves. Ischemia produced enhancement of breathing followed by apnea and gasping. During enhanced breathing as well as during gasping, the inspiratory-inhibiting effect of lung inflation (Breuer-Hering reflex) was abolished. When brain circulation was restored, respiratory activity started with gasps, which later were intermingled with eupneic type of inspirations. During the onset of a eupneic breath, lung inflation produced inspiratory facilitation but never an inhibition. However, after 30 min of recovery from cerebral ischemia, the Breuer-Hering reflex was restored. Results show that precise analysis of vagal reflexes and respiratory pattern during ischemia and resuscitation may be used as an indicator of resumption of autonomic activity in the brain stem.

Breathing patterns in patients with chronic obstructive pulmonary disease.

The respiratory inductance plethysmograph (RIP) was used to record resting breathing for 45 min in 12 patients with stable chronic obstructive pulmonary disease (COPD) and 8 age- and sex-matched control subjects. The COPD group had mean FEV1.0 of 31% predicted (range: 15 to 49%), mean PaO2 of 70 mmHg (56 to 83 mmHg), and mean PaCO2 of 37 mmHg (31 to 47 mmHg). All subjects were studied in the sitting position, and the rib cage (RC) and abdomen (ABD) RIP signals were simultaneously recorded on a polygraph and sampled at 20 Hz by a microcomputer. The summed RC and ABD signals were processed to create a spirogram from which the timing components of the respiratory cycle were subsequently analyzed. The mean number of breaths analyzed per subject was 702 +/- 213 (SD). Mean tidal volumes were identical in both groups. Inspiratory and expiratory times were significantly less (p less than 0.01), and mean inspiratory flow was significantly greater (p less than 0.01) in the COPD group. Frequency and minute ventilation also were significantly greater in the COPD group (p less than 0.005). Variability of breathing pattern, assessed in terms of coefficients of variation, was significantly less for TI, TI/Ttot, and VI in COPD patients than in normal subjects, even after sighs had been excluded from the analysis. We suggest that alterations in breathing pattern and its variability reflect changes in neural control of breathing consequent to disease.