The nervous mechanisms that generate swallowing are still largely unknown. It has been suggested that a central pattern generator that contains a serial network of linked neurons must produce the successive excitation of motoneurons (Mns) and then the sequential activation of muscle through excitatory connections. Inhibitory connections have also been envisioned but never evidenced at the membrane level of the swallowing neurons. We investigated, by intracellular recordings, the behavior of 96 Mns in the rostral nucleus ambiguus during swallowing induced by application of superior laryngeal nerve stimulation to anesthetized sheep. The Mns were identified by antidromic activation following stimulation of glossopharyngeal, pharyngoesophageal, or cervical vagal nerves. Nine Mns showed a bell-shaped depolarization during the buccal or the early pharyngeal stage of swallowing. They probably projected to muscles of the soft palate (palatopharyngeal) and upper pharynx (stylopharyngeal, hyopharyngeal). Thirty-eight Mns exhibited a chloride-dependent hyperpolarization, indicating that they were under an active inhibition throughout the buccopharyngeal stage of swallowing. These Mns constitute a heterogeneous pool: some of them, producing spontaneous inspiratory discharges, probably innervated laryngeal or pharyngeal muscles; others might also be Mns of the esophagus, whose swallowing pattern was modified because of the anesthesia (suppression of the esophageal peristalsis). Forty-nine Mns showed a chloride-dependent hyperpolarization with a variable duration at the onset of swallowing, followed by a depolarization that could take place during either the buccopharyngeal (HD1-Mns) or the esophageal (HD2- and HD3-Mns) stage of deglutition. HD1-Mns probably projected to the median and inferior constrictors of the pharynx. HD2-Mns produced depolarizations with longer latencies and durations than those of the HD1-Mns. They probably projected to either the superior esophageal sphincter or the cervical esophagus (CE). HD3-Mns showed a buccopharyngeal hyperpolarization that was followed first by a lower-amplitude hyperpolarization accompanying the proximal CE contraction and then by a delayed depolarization. These Mns probably innervated the inferior CE or thoracic esophagus. We conclude that the initial inhibition exerted on the HD-Mns, by delaying the excitation of Mns, may play a role in the nervous mechanisms involved in temporal organization of the swallowing motor sequence. We suggest that swallowing disorders in humans such as dysphagia by failure of cricopharyngeal relaxation, diffuse esophageal spasm, and achalasia might be caused by impaired inhibitory mechanisms.

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We investigated in sheep the effects of stimulation of the thick afferent fibers running through the lingual nerve (LN) upon the activity of some of the muscles and medullary interneurons or motoneurons which are active during swallowing. Using electromyography (EMG), and extra- and intracellular neuronal recording, we demonstrated that LN stimulation inhibited triggering and/or distal progression of deglutition reflexly induced by stimulation of the superior laryngeal nerve (SLN). This inhibition appeared as a delay, or the interruption or total suppression, of the EMG and neuronal swallowing activities, depending on the interval between SLN and LN stimulation. It was apparent at the level of the muscles and motoneurons of the nucleus ambiguus, as well as at the level of the interneurons of the dorsal medulla within or around the nucleus of solitary tract, which are assumed to be the core of the organizing system for swallowing, the so-called central pattern generator (CPG). Taking into account the stimulation parameters used in our experiments, it was likely that only LN-mechanosensitive fibers were excited. These fibers were involved in the jaw-opening reflex, and possibly in mastication regulation. Therefore, inhibition of swallowing could result from interactions between the hindbrain mastication and swallowing CPGs. However, it was also possible that mechanosensitive afferents acted upon the swallowing CPG directly or indirectly through supramedullary, especially cortical, loops.

The role of acetylcholine in the central mechanism of swallowing remains a matter of debate. The aim of this work, conducted in sheep, was to assess the effects of anti-muscarinic drugs (mainly atropine) on the activity of peripheral muscles involved in the oropharyngeal and esophageal phases of swallowing, and on that of dorsal medulla interneurons which program swallow-induced esophageal contractions and therefore belong to the so-called central pattern generator. Our results were obtained in anesthetized animals by means of electromyographic and manometric recordings of peripheral muscle contractions associated with microelectrode recordings of medullary interneuron discharge. They show that both interneuron discharge and primary esophageal contractions that follow the oropharyngeal component of swallowing were suppressed under atropine (0.1--0.5 mg/kg). In contrast, atropine did not impede the swallowing oropharyngeal component, the secondary peristalsis and the "deglutitive inhibition," which affects the esophageal motility during the oropharyngeal phase of swallowing. In conclusion, muscarinic receptors (probably not those of M(1)type) appear to control the primary peristalsis, but neither the secondary peristalsis nor the deglutitive inhibition.