Читать книгу The Esophagus - Группа авторов - Страница 117

Once the swallowing process is initiated at any stage, sequential activation of the neurons in the remaining portions of the swallowing pathway occurs [7, 18, 35]. Although sequential activation of neurons along the program is the basis for the eventual pattern of motor events in each peripheral location, inhibitory messaging is also present along the entire program circuitry. As swallowing proceeds down the esophagus, excitation decreases along the program pathway while inhibition correspondingly increases; this is also reflected in the concentration of excitatory and inhibitory neurotransmitters along the esophagus [36]. The decreasing excitation increases the role of sensory feedback to shape the activity of the central program depending on the bolus requirements (Figure 5.2). In the esophageal stage, sensory feedback may also be necessary to further excite the esophageal stage of the program for muscle contraction and peristalsis to occur [37–42].

Inhibition within and along the SPG serves at least two purposes: timing of peristalsis by progressively delaying excitation distally along the circuitry, and deglutitive inhibition of motor events to allow repetitive swallowing [36]. Excitation of neurons at any stage in the esophageal program circuitry shuts down activity in all neurons destined for more distal esophageal sites. Excitation at any peripheral level increases excitation at the corresponding level in the SPG while also increasing inhibition below that SPG level.

The oral‐to‐pharyngeal stage connection and the DSG‐to‐VSG motor neuron activation pathway are well established for the oropharyngeal stages of swallowing and appear fairly consistent among different species, regardless of the esophageal muscle type. It remains unknown if the connection of the pharyngeal stage to the esophageal circuitry from the DSG program in the NTS_ce to the motor neurons for the esophagus is direct or through a VSG [7, 35].

While there are numerous transmitter mechanisms within the SPG [35], only a few are responsible for the major actions. Excitation is mediated by excitatory amino acids such as glutamine and by the cholinergic system, while inhibition is through the action of gamma‐butyric acid (GABA) acting at the GABA_A receptor. Nicotinic action is important for activation of premotor neurons in the programming and organizing portions of the SPG, while muscarinic action appears to couple the oropharyngeal with the esophageal stages of the SPG and activate motor neurons. At the level of the NTS_ce, two other transmitters are important in activation of the esophageal and LES neurons: nitric oxide (NO) and somatostatin. NO is involved with regulating esophageal contraction amplitude and LES tone and contraction [43, 44]. Other transmitters such as serotonin, norepinephrine, oxytocin, and vasopressin have modulatory roles and are likely also to influence other interrelated functions such as hunger, thirst, nausea, and sleep.

Figure 5.2 Excitation and inhibition in the swallowing network. (A) The swallowing network can be seen as a chain of neurons with excitatory (triangles) and inhibitory (dots) connections, and sensory feedback (broken lines). The power of excitatory inputs decreases along the chain; that of inhibitory inputs increases and can lead to long periods of inhibition of neurons controlling more distal parts of the tract. (B) The central pattern generator can be divided into an oropharyngeal network and an esophageal network. The esophageal network is first inhibited (dot) and then excited (triangle) to provide for successive activation of esophageal neurons. (C) Inhibitory–excitatory sequence recorded in an esophageal motor neuron in the sheep. (i) A single swallow was induced by stimulation of the superior laryngeal nerve (SLN). A biphasic inhibitory hyperpolarization was followed by a depolarization. (ii) When spiking occurs on the after‐depolarization, a contraction occurs following the inhibitory delay.

Source: Jean [7] with permissions of Springer Nature.