Cerebellar modulation of cough motor pattern in cats

Xu, Fadi, Donald T. Frazier, Zhong Zhang, David M. Baekey,and Roger Shannon. Cerebellar modulation of cough motor pattern incats. J. Appl. Physiol. 83(2):391-397, 1997.The cerebellum modulates respiratory muscleactivity in part via its influence on the central respiratory patterngenerator. Because coughing requires well-coordinated respiratorymuscle activity, studies were conducted to determine whether thecerebellum influences the centrally generated cough motor pattern.Integrated phrenic and lumbar efferent neurograms(PN and LN, respectively)were monitored in decerebrated, paralyzed, and ventilated cats.Mechanical probing of the intrathoracic trachea was used to evokefictive coughs; i.e., large increases inPN and LN amplitudes.Cerebellectomy resulted in a decrease in the number of coughsper trial (cough frequency) and LN peakamplitudes without any consistent change inPN peak amplitudes. Cerebellar nuclei [therostral interposed nucleus (INr) and the rostral fastigial nucleus(FNr)] known to be involved in respiratory control were ablatedto determine their potential role in the cough response. Control(eupneic) respiratory frequency was not affected by cerebellectomy orINr/FNr lesions. Cough frequency was depressed by lesion of the INr butnot by ablation of the FNr. No significant changes inPN and LN amplitudes wereobserved after lesion of either the INr or FNr. These results suggestthat the cerebellum, specifically the INr, is involved in modulation ofthe frequency of centrally generated coughing.

     

Ventrolateral medullary respiratory network and a model of cough motor pattern generation

The primaryhypothesis of this study was that the cough motor pattern is produced,at least in part, by the medullary respiratory neuronal network inresponse to inputs from "cough" and pulmonary stretch receptorrelay neurons in the nucleus tractus solitarii. Computer simulations ofa distributed network model with proposed connections from the nucleustractus solitarii to ventrolateral medullary respiratory neuronsproduced coughlike inspiratory and expiratory motor patterns. Predictedresponses of various "types" of neurons (I-DRIVER, I-AUG, I-DEC,E-AUG, and E-DEC) derived from the simulations were tested in vivo.Parallel and sequential responses of functionally characterizedrespiratory-modulated neurons were monitored during fictive cough indecerebrate, paralyzed, ventilated cats. Coughlike patterns in phrenicand lumbar nerves were elicited by mechanical stimulation of theintrathoracic trachea. Altered discharge patterns were measured in mosttypes of respiratory neurons during fictive cough. The resultssupported many of the specific predictions of our cough generationmodel and suggested several revisions. The two main conclusions were asfollows: 1) TheBötzinger/rostral ventral respiratory group neurons implicated inthe generation of the eupneic pattern of breathing also participate inthe configuration of the cough motor pattern.2) This altered activity ofBötzinger/rostral ventral respiratory group neurons istransmitted to phrenic, intercostal, and abdominal motoneurons via thesame bulbospinal neurons that provide descending drive during eupnea.

     

Effects of antitussive drugs under normal and pathological conditions

The antitussive effect codeine and 1-propoxyphene have been studied in non-anaesthetized healthy cats and cats with respiratory tract inflammation elicited by undiluted croton oil. The drugs were administered intraperitoneally in doses of 10 and 20 mg/kg body weight. The antitussive effect was studied on the 4th day, after inflammation had set in. Cough induced in nonanaesthetized cats by mechanical irritation of the laryngopharyngeal and tracheobronchial areas was evaluated by changes of the lateral tracheal pressure. Experimentally induced inflammatory changes of the respiratory tract due to the antitussive activity of 1-porpoxyphene were significantly reduced, but that of codeine had not changed at all.     

GABA-ergic mechanisms in the central control of cough

The antitussive activity of gabalinoleamide (Gabalid U CB) was studied in 40 non-anaesthetized cats. The antitussive action of the substance was compared to that of codeine (Codein Spofa). Cough was induced by mechanical stimulation using a chronic tracheal cannula. Single cough parameters were evaluated from changes in the side tracheal pressure. When gabalinoleamide was administered in a dose of 100 mg/kg b.w. intramuscularly all the studied parameters of cough showed a statistically significant decrease, only the intensity of maximum cough effort remained unaffected. Gabalinoleamide administered in the same dose induced a statistically significant decrease of respiratory frequency and breathing amplitude, and prolonged the cycle of breathing by delaying the expiratory phase. Higher doses (200 and 300 mg/kg b.w.) did not have an increased cough suppressing effect. The quality and quantity of cough parameters were similar after codeine and gabalinoleamide.     

Abdominal ventilatory pattern in crickets depends on the stridulatory motor pattern

Abstract. Ventilatory motor patterns were recorded from abdominal muscles in crickets, Gryllus campestris L.and Teleogryllus commodus (Walker), at rest and during three types of stridulatory motor activity; calling, courtship and aggressive song.
Increases in ventilatory period were almost exclusively due to an increase of the pause between expiratory bursts, whereas abdominal ventilatory bursts remained constant at 200 ms.Ventilatory patterns depended on the stridulatory motor pattern and indicated that the same basic respiratory oscillator exists in both cricket species.
In G.campestris there was a strict 1:1 coupling between chirps and ventilatory bursts.In T.commodus such a relationship was also observed for the chirp part of the songs, but less strictly for the trill part of the calling song and not for the courtship song.In both species the onset of the ventilatory burst was within ± 100 ms of a stridulatory chirp.Ventilatory burst lasted longer the earlier they began before a stridulatory chirp.This suggests strongly that the stridulatory motor pattern terminates the expiratory burst, and thus influences the ventilatory motor pattern.     

Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit

We have previously shown that ionotropic glutamate receptors in the caudal portion of the nucleus tractus solitarii (NTS), especially in the commissural NTS, play a prominent role in the mediation of tracheobronchial cough and that substance P potentiates this reflex. This NTS region could be a site of action of some centrally acting antitussive agents and a component of a drug-sensitive gating mechanism of cough. To address these issues, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30-50 nl) of centrally acting antitussive drugs into the caudal NTS of pentobarbitone-anesthetized, spontaneously breathing rabbits. [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and baclofen decreased baseline respiratory frequency because of increases in the inspiratory time only at the higher concentration employed (5 mM and 1 mM, respectively). DAMGO (0.5 mM) and baclofen (0.1 mM) significantly decreased cough number, peak abdominal activity, peak tracheal pressure, and increased cough-related total cycle duration. At the higher concentrations, these agents suppressed the cough reflex. The effects of these two drugs were counteracted by specific antagonists (10 mM naloxone and 25 mM CGP-35348, respectively). The neurokinin-1 (NK1) receptor antagonist CP-99,994 (10 mM) abolished cough responses, whereas the NK2 receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the caudal NTS is a site of action of some centrally acting drugs and a likely component of a neural system involved in cough regulation. A crucial role of substance P release in the mediation of reflex cough is also suggested.     

Changing pattern of drugs used for self-poisoning.

In 1967-76 the annual number of admissions to a poisoning treatment centre rose from 964 to 2134. The proportion of admissions caused by taking barbiturate hypnotics and methaqualone fell considerably while that caused by taking benzodiazepines and tricyclic antidepressants increased. As a result the proportion of patients admitted unconscious fell from 23% to 15%. The declining contributions of barbiturates and methaqualone and increased importance of tricyclic antidepressants were significant in all grades of coma. The change in drugs taken, however, has not yet reduced the percentage of unconscious patients needing endotracheal intubation or assisted ventilation, and hypothermia remains as common. Only hypotension has become less frequent as antidepressants replace barbiturates as the main cause of drug-induced coma. The use of salicylates for self-poisoning is declining slowly, and paracetamol poisoning is now as common.     

Locomotion in the pulmonate snail Melampus--I. The motor pattern

1. The patterned neural activity that drives muscular locomotor movements in Melampus is generated within the central nervous system. 2. In the transition from quiescent state to crawling, the pattern recorded in nerves and connectives changes from short-duration bursts in many units to the 60-100 sec cycle of events recorded during tethered crawling in the semi-intact snail. 3. Extracellularly recorded bursts and individually recognizable spikes in pedal nerves are correlated with movements that occur at each stage of the cyclically repeated crawl-steps. 4. Intracellularly recorded pedal neurons involved in locomotion receive excitatory drive, inhibitory drive, or alternating excitatory and inhibitory drive during the step cycle.     

Altering cAMP levels within a central pattern generator modifies or disrupts rhythmic motor output

Cyclic AMP is a second messenger that has been implicated in the neuromodulation of rhythmically active motor patterns. Here, we tested whether manipulating cAMP affects swim motor pattern generation in the mollusc, Tritonia diomedea. Inhibiting adenylyl cyclase (AC) with 9-cyclopentyladenine (9-CPA) slowed or stopped the swim motor pattern. Inhibiting phosphodiesterase with 3-isobutyl-1-methylxanthine (IBMX) or applying dibutyryl-cAMP (dB-cAMP) disrupted the swim motor pattern, as did iontophoresing cAMP into the central pattern generator neuron C2. Additionally, during wash-in, IBMX sometimes temporarily produced extended or spontaneous swim motor patterns. Photolysis of caged cAMP in C2 after initiation of the swim motor pattern inhibited subsequent bursting. These results suggest that cAMP levels can dynamically modulate swim motor pattern generation, possibly shaping the output of the central pattern generator on a cycle-by-cycle basis.     

Significance of the pattern of motor innervation of the intrinsic laryngeal muscles of cat.

Simple and compound forms of motor endings, showing a particular distribution, were found in the intrinsic laryngeal muscles of the cat. The muscles carrying compound and multiple endings were stained densely black with Sudan black B; while the muscles with simple and single endings showed black and pale fibres. A probable relationship is suggested between the contraction properties and the pattern of motor innervation of intrinsic laryngeal muscles of the cat.     

Descending influences on escape behavior and motor pattern in the cockroach

The escape behavior of the cockroach is a ballistic behavior with well characterized kinematics. The circuitry known to control the behavior lies in the thoracic ganglia, abdominal ganglia, and abdominal nerve cord. Some evidence suggests inputs may occur from the brain or suboesophageal ganglion. We tested this notion by decapitating cockroaches, removing all descending inputs, and evoking escape responses. The decapitated cockroaches exhibited directionally appropriate escape turns. However, there was a front-to-back gradient of change: the front legs moved little if at all, the middle legs moved in the proper direction but with reduced excursion, and the rear legs moved normally. The same pattern was seen when only inputs from the brain were removed, the suboesophageal ganglion remaining intact and connected to the thoracic ganglia. Electromyogram (EMG) analysis showed that the loss of or reduction in excursion was accompanied by a loss of or reduction in fast motor neuron activity. The loss of fast motor neuron activity was also observed in a reduced preparation in which descending neural signals were reversibly blocked via an isotonic sucrose solution superfusing the neck connectives, indicating that the changes seen were not due to trauma. Our data demonstrate that while the thoracic circuitry is sufficient to produce directional escape, lesion or blockage of the connective affects the excitability of components of the escape circuitry. Because of the rapidity of the escape response, such effects are likely due to the elimination of tonic descending inputs.