Morton I. Cohen

Switching of the respiratory phases and evoked phrenic responses produced by rostral pontine electrical stimulation

1. In midcollicular‐decerebrate, gallamine‐paralysed, vagotomized cats, efferent phrenic discharge was recorded as an indicator of the central respiratory cycle. Electrical stimulation (50–250/sec) delivered in the rostral lateral pontine ‘pneumotaxic centre’ region (in and near nucleus parabrachialis), and set to occur at specified times in the cycle, produced powerful respiratory effects: (a) at dorsolateral points, inspiratory‐facilitatory effects (increase of phrenic discharge, shortening of the expiratory phase); (b) at ventrolateral points, expiratory‐facilitatory effects (decrease of phrenic discharge, shortening of the inspiratory phase, lengthening of the expiratory phase).

High-frequency and medium-frequency components of different inspiratory nerve discharges and their modification by various inputs.

In decerebrate paralyzed cats, spectral analysis was performed on simultaneous recordings of efferent inspiratory nerves (phrenic, recurrent laryngeal, hypoglossal). Spectral peaks were present both in the high-frequency (HFO) range (50-100 Hz) and the medium-frequency (MFO) range (20-50 Hz). Different activities were coherent only in the HFO range, indicating that the HFOs arise in a common inspiratory pattern generator that drives the different motoneuron populations, whereas the MFOs are specific to different systems.

Afferent projections to the inspiratory neuronal region of the ventrolateral nucleus of the tractus solitarius in the cat.

Brain stem neurons with an inspiratory (I) modulated pattern of discharge are found concentrated in the regions of the ventrolateral nucleus of the tractus solitarius (vlNTS) 1,2,5,9, the nucleus retroambigualis rostral to the obex (rNRA) ~,15 and the nucleus parabrachialis medialis (NPBM) in the dorsolateral rostral pons4, s. However, since the sites of respiratory modulated neuronal activity (identified electrophysiologically) have not been demonstrated to be isomorphic with these anatomical structures, we will refer to the populations of respiratory neurons found in the vicinity of the vlNTS, rNRA and NPBM as the dorsal respiratory group (DRG)Z, ~, and ventral respiratory group (VRG)Z, and pneumotaxic center (PC) 4, respectively. The different populations of I neurons have similar periodic firing patterns; they must, therefore, ultimately be connected. Recently, interest has focused on connections of the I neurons of the DRG. These neurons are believed to play an important role in the generation of the respiratory pattern, since: (a) about 80 ~ have spinal cord axons that project to the level of phrenic motoneurons2, 5 and many have short latency excitatory inputs to contralateral phrenic motoneurons7,1°; (b) about half receive excitatory inputs from the pulmonary stretch receptors that are involved in the Breuer-Hering 1-inhibitory reflex2,9,13; and (c) small lesions in the v lNTS result in apneusis 11. Our knowledge of the brain stem connections of the D R G is limited. Merrill identified efferent projections from the D R G to the VRG using antidromic stimulation16; this physiological result has been supported by neuroanatomical studies (Feldman and Meibach, unpublished observations and ref. 14). Merrill has also stated that with microstimulation techniques he could not find any afferents to the D R G from the VRG 16. If no such projections exist, the respiratory modulation of units in in the D R G in the vagotomized decerebrate animal could not be due to any rhythmic afferent input and therefore must be intrinsic to that group. Therefore, several authors

Properties of inspiratory termination by superior laryngeal and vagal stimulation

Electrical stimulation of two respiratory afferent nerves, the vagus and the internal branch of the superior laryngeal, was used to terminate inspiration. The short latency responses of phrenic motoneurones to these stimuli were studied to determine if inspiratory termination was preceded by a characteristic phrenic motoneurone discharge pattern, reflecting changes in brainstem inspiratory neurone discharge and inspiratory terminating mechanisms. Stimulus trains of sufficient intensity delivered to the superior laryngeal nerve terminated inspiration within 50 ms and were preceded by a stereotyped pattern of phrenic motoneurone discharge. This consisted of a short latency (disynaptic), predominantly contralateral excitation in response to the first shock of the train, followed by a marked and long lasting inhibition. In contrast, vagal stimulation typically terminated inspiration hundreds of milliseconds after the onset of the stimulus train and was not preceded by a stereotyped pattern of phrenic motoneurone responses to single shocks. Transient short latency responses were obtained but were extremely small, requiring considerable excitation followed by a moderate bilateral depression of activity. Inspiration could be terminated with or without the presence of these short latency responses. These results indicate that superior laryngeal and vagal (presumably pulmonary stretch receptor) afferents have different projections to brainstem inspiratory neurones and may exert their effects on inspiratory duration through different, but as yet undefined, neural mechanisms.

Hypoglossal motoneuron responses to pulmonary and superior laryngeal afferent inputs

In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, the inspiratory discharges of the hypoglossal (whole nerve or single fibers), phrenic, and recurrent laryngeal nerves were compared, and the effects of pulmonary and superior laryngeal afferent inputs were observed. During lung inflations in phase with neural inspiration, hypoglossal and recurrent laryngeal activities differed from phrenic with respect to (a) burst onset times: both preceded the phrenic; (b) overall pattern: phrenic, augmenting; hypoglossal, decrementing; recurrent laryngeal, plateau-like. When inflation was withheld, the phrenic pattern was not markedly changed, but both hypoglossal and recurrent laryngeal became augmenting; the marked increase of hypoglossal activity (both whole nerve and single fiber) indicated strong inhibition by lung afferents. Superior laryngeal electrical stimulation evoked excitation of the contralateral phrenic (latency 4.1 msec) and the ipsilateral whole hypoglossal (latency 5.3 msec), followed by bilateral inhibitions (durations 20-30 msec); most hypoglossal fibers showed only inhibition. We conclude that, although both hypoglossal and phrenic outputs are driven by the inspiratory pattern generator(s), their promotor systems differ with respect to influences from central and peripheral inputs.

Inspiratory-modulated neurons of the rostrolateral pons: effects of pulmonary afferent input.

In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, firing of inspiratory (I) and I-modulated neurons in the pontine respiratory group was markedly increased by withholding lung inflation, indicating strong inhibition by lung afferents. Spectral analysis showed that only a small minority of I-modulated neurons had high-frequency oscillations (HFO), in contrast to medullary I neurons, indicating that the pontine neurons are not closely linked to medullary I networks.

Changes in frequency content of inspiratory neuron and nerve activities in the course of inspiration

In decerebrate paralyzed cats, the spectra and coherences of inspiratory (I) nerve activities and of medullary I neuron discharges were compared between different stages of I. The correlated high-frequency oscillations (HFOs) in the activities had common time courses of frequency and strength, which were influenced by lung afferent input; whereas the time courses for the uncorrelated medium-frequency oscillations (MFOs) depended on individual activity patterns. These results indicate that HFOs are characteristic of the common I pattern generator, whereas MFOs are specific to individual activities.

Fast rhythms in the discharges of medullary inspiratory neurons.

The discharges of 44 medullary inspiratory (I) neurons in decerebrate paralyzed cats were studied using interval and spectral analysis. Most neurons had a rhythm in their discharge. In 31 the rhythm was at the frequency of, and coherent to, the high-frequency oscillations (HFOs) of I nerves, and in 7 the rhythm was in the range of medium-frequency oscillations (MFOs), with no coherence to nerve MFOs. Thus, correlated HFOs are characteristic of the I system at all levels, whereas MFOs are uncommon in medullary neurons and seem to be unrelated to general mechanisms.

Fast (3 Hz and 10 Hz) and slow (respiratory) rhythms in cervical sympathetic nerve and unit discharges of the cat

1 In seven decerebrate cats, recordings were taken from the preganglionic cervical sympathetic (CSy) nerves and from 74 individual CSy fibres. Correlation and spectral analyses showed that nerve and fibre discharges had several types of rhythm that were coherent (correlated) between population and unit activity: respiratory, ‘3 Hz’ (2–6 Hz, usually cardiac related), and ‘10 Hz’ (7–13 Hz). 2 Almost all units (73/74) had respiratory modulation of their discharge, either phasic (firing during only one phase) or tonic (firing during both the inspiratory (I) and expiratory (E) phases). The most common pattern consisted of tonic I‐modulated firing. When the vagi were intact, lung afferent input during I greatly reduced CSy unit and nerve discharge, as evaluated by the no‐inflation test. 3 The incidence of unit‐nerve coherent fast rhythms (3 Hz or 10 Hz ranges) depended on unit discharge pattern: they were present in an appreciable fraction (30/58 or 52 %) of tonic units, but in only a small fraction (2/15 or 13 %) of phasic units. 4 When baroreceptor innervation (aortic depressor amd carotid sinus nerves) was intact, rhythms correlated to the cardiac cycle frequency were found in 20/34 (59 %) of units. The cardiac origin of these rhythms was confirmed by residual autospectral and partial coherence analysis and by their absence after baroreceptor denervation. 5 The 10 Hz coherent rhythm was found in 7/34 units when baroreceptor innervation was intact, where it co‐existed with the cardiac‐locked rhythm; after barodenervation it was found in 9/50 neurones. Where both rhythms were present, the 10 Hz component was sometimes synchronized in a 3:1 ratio to the 3 Hz (cardiac‐related) frequency component. 6 The tonic and phasic CSy units seem to form distinct populations, as indicated by the differential responses to cardiac‐related afferent inputs when baroreceptor innervation is intact. The high incidence of cardiac‐related correlation found among tonic units suggests that they are involved in vasomotor regulation. The high incidence of respiratory modulation of discharge suggests that the CSy units may be involved in regulation of the nasal vasculature and consequent ventilation‐related control of nasal airway resistance.

Responses or recurrent laryngeal motoneurons to changes of pulmonary afferent inputs

In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, the discharges of the recurrent laryngeal (whole nerve or single fibers) and phrenic nerves, and the changes produced by pulmonary afferent inputs (lung inflation), were compared. When lung inflation was in phase with neural inspiration, four types of laryngeal fiber activities were observed: (a) phasic-inspiratory; (b) tonic-inspiratory; (c) expiratory-inspiratory; (d) early-expiratory. The firing patterns during inspiration were plateau-like, whereas the phrenic pattern was augmenting. When inflation was withheld, the plateau patterns usually became augmenting, indicating inhibition of laryngeal inspiratory activity by pulmonary afferents. Secondary effects of withholding inflation were (a) increases of early-expiratory activity (both whole nerve and individual fiber), indicating increased post-inhibitory rebound excitation; (b) decreased activity of tonic-inspiratory and expiratory-inspiratory fibers during early neural expiration, indicating increased inhibition by early-expiratory neurons. The discharge patterns of different types of laryngeal motoneuron, as well as their changes with inflation, are interpreted in relation to the function of regulating airway resistance.