Role of midbrain in the control of breathing in anuran amphibians

The present study was designed to explore systematically the midbrain of unanesthetized, decerebrate anuran amphibians (bullfrogs), using chemical and electrical stimulation and midbrain transections to identify sites capable of exciting and inhibiting breathing. Ventilation was measured as fictive motor output from the mandibular branch of the trigeminal nerve and the laryngeal branch of the vagus nerve. The results of our transection studies suggest that, under resting conditions, the net effect of inputs from sites within the rostral half of the midbrain is to increase fictive breathing frequency, whereas inputs from sites within the caudal half of the midbrain have no net effect on fictive breathing frequency but appear to act on the medullary central rhythm generator to produce episodic breathing. The results of our stimulation experiments indicate that the principal sites in the midbrain that are capable of exciting or inhibiting the fictive frequency of lung ventilation, and potentially clustering breaths into episodes, appear to be those primarily involved in visual and auditory integration, motor functions, and attentional state.

Mechanism of respiratory arrest in an animal model of acute fatal bronchoconstriction

The cause of respiratory arrest in acute asthma is not known. By its nature, respiratory arrest is difficult to study clinically. The possible causes of respiratory arrest include cardiovascular dysfunction, respiratory muscle fatigue, and central respiratory failure. We used a dog model of respiratory arrest in acute bronchoconstriction that examined the effects of hypoxemia and intrinsic loading in an attempt to establish the mechanism. Our hypothesis was that, in a setting of hypoxemia and intrinsic loading similar to human fatal asthma, respiratory arrest is caused by a central respiratory failure, more specifically, failure of the central rhythm generator. We studied 18 dogs divided into 1) an intrinsically loaded group, 2) a hypoxemic group, and 3) both a loaded and a hypoxemic group. Intrinsic loading was induced with methacholine combined with selective beta 2-blockade, and the hypoxemia was controlled by varying inspired O2 fraction. Respiratory arrest occurred only in animals with both hypoxemia and intrinsic loading. We found no evidence of hemodynamic instability or respiratory muscle fatigue. Instead, there was an abrupt cessation of ventilation while the intensity of the central neural output was maintained. Our results are consistent with a failure of the central rhythm generator as the causal agent in respiratory arrest.

Localization of central rhythm generator involved in cortically induced rhythmical masticatory jaw-opening movement in the guinea pig

The location of the central rhythm generator involved in the cortically induced rhythmical masticatory jaw-opening movement was studied in the ketamine-anesthetized guinea pig. These studies show that a population of neurons is activated by a nonrhythmical input from the cortical masticatory area (CMA) and produces a rhythmical output to the trigeminal motoneurons innervating the jaw-opening muscles. Repetitive stimulation (30 Hz) of the pyramidal tract (PT) rostral to the middle level of the medulla oblongata, in the animal with a precollicular transection as well as with an intact neuraxis, induced a rhythmical reciprocal EMG activity in the anterior digastric and masseter muscles. The rhythmical activity could be monitored by a rhythmical burst in the efferent discharge in the mylohyoid nerve innervating the anterior digastric muscle. Essentially the same pattern was observed when stimulating the PT as that induced by repetitive stimulation of the CMA. The rhythmical efferent burst in the mylohyoid nerve could still be induced after paralyzing the animal. Repetitive PT stimulation in the isolated brain stem after precollicular and bulbospinal transections induced a rhythmical pattern in the anterior digastric EMG and an efferent activity in the mylohyoid nerve. The rhythmical mylohyoid nerve burst could be induced after paralyzing the animal. After section of the medial part of the brain stem at the pontobulbar junction, including the PT, repetitive PT stimulation at the pontine level did not induce any masticatory activity either in the digastric EMG or in the efferent discharge in the mylohyoid nerve, while stimulation at the rostral bulbar level still induced a rhythmicity that was essentially the same pattern as before the section. By testing the effects of total and partial transections of the brain stem in coronal and sagittal planes at various locations, we found that the medial bulbar reticular formation, the lateral pons including the trigeminal motor nucleus and nerve, and the reticulotrigeminal motoneuronal pathways composed the minimum structures that must be left intact to induce a rhythmicity in the anterior digastric EMG and the efferent discharge in the mylohyoid nerve by repetitively stimulating the PT. Repetitive PT stimulation induced a field potential in the medial bulbar reticular formation, which periodically fluctuated in the masticatory rhythm coincident with the rhythmical activity in the digastric EMG. This fluctuation persisted in the same rhythm after paralysis of the animal.(ABSTRACT TRUNCATED AT 400 WORDS)

SUPRACHIASMATIC LESIONS DISRUPT THE DAILY RHYTHMICITY IN THE SEXUAL BEHAVIOUR OF NORMAL MALE RATS AND OF MALE RATS TREATED NEONATALLY WITH ANTIOESTROGEN

Male rats were treated daily with oil or 100 μg of the antioestrogen, ethamoxytriphetol (MER-25), for the first 10 days of life and, when adult, lesions were made in the suprachiasmatic nuclei (SCN) of the hypothalamus or control lesions were made above the SCN and the rats were tested for sexual behaviour. Treatment with MER-25 enhanced the daily rhythmicity in both mounting and lordosis behaviour and SCN lesions disrupted these behavioural rhythms and the rhythm in the mounting behaviour of oil-treated rats. Rats treated with MER-25 and with SCN lesions showed high levels of mounting and lordosis behaviour throughout the light: darkness cycle. These results support the hypothesis that sexual differentiation by perinatal androgen stimulation uncouples the central rhythm generator from the neural substrates of sexual behaviour in rats.

Central Programming and Reflex Control of Walking in the Cockroach

1. The activity in identified motor units supplying the coxal levator and depressor muscles of the cockroach have been recorded in intact freely walking animals and in preparations after removal of all sensory input from leg receptors. 2. Reciprocal activity in levator and depressor motoneurones can be evoked, or occurs spontaneously, in the partially de-afferented preparations, thus indicating the existence of a central locomotory rhythm generator. 3. The reciprocal activity patterns recorded in the same motoneurones in intact freely moving animals are not identical to those recorded in partially de-afferented preparations. Thus, the production of normal rhythmic leg movements depends to some extent on sensory input from leg receptors, this input probably exerting tonic and phasic effects on the central rhythm generator. 4. An increase in the resistance to leg retraction during normal walking results in an increase in discharge rate of the levator and depressor motoneurones. This observation further demonstrates that rhythmic leg movements are not exclusively centrally controlled. The receptors responsible for this reflex effect are probably the trochanteral campaniform sensilla.