Effects of NMDAR Antagonists on Swallow and Laryngeal Adductor Reflex

Swallowing is a behavior that requires the well-formed coordination of a series of muscles to convey a bolus of food/liquid down the esophagus. These muscles are controlled by motoneurons in different areas of the hindbrain and spinal cord and are also the target of other brainstem circuits such as respiratory networks. We conducted experiments in anesthetized, spontaneously breathing cats to determine effects of NMDAR antagonists on water-solicited swallow, as well as swallows elicited by high frequency electrical stimulation of the superior laryngeal nerve (SLN) while recording electromyograms from pharyngeal, laryngeal, and respiratory-related muscles. We recently showed that when kynurenic acid, an endogenously produced metabolite of the essential amino acid tryptophan that may block NMDARs, was injected into the rostral nucleus tractus solitarius (NTS) bilaterally it inhibited the coherent production of swallow from pharyngeal water stimuli. Here, we show that intra-arterial or intravenous delivery of the non-competitive NMDA receptor blocker, MK-801, also inhibits swallows elicited from both pharyngeal water stimuli as well as high-frequency SLN stimulation. Interestingly, this drug has limited effects on the elemental laryngeal adductor reflex (LAR) elicited from lower frequency stimulus of the SLN, which is clinically used to evaluate vocal fold function. Finally, we also illustrate a simplified computational model of various hindbrain neuronal populations and a connectivity scheme that qualitatively supports the above experimental data with fictive SLN electrical stimulation: that is, a shorter NMDAR-agnostic LAR pathway to nucleus ambiguus and hypoglossal motor pathways driving upper airway muscles and a polysynaptic pathway that relies on NMDARs to promote the production of reflex swallow bursts. The model also supports an avenue for competitive interactions of these swallow-related microcircuits with a subnetwork that produces respiratory rhythms. These data support the notion that NMDARs are normally an important element in the production of reflex swallow, but not LAR, in vivo. This work was supported by the NIH HL155721, NIH HL163008, NLHB HL103415, VEGA Project 1/0072/16, and VEGA Project 1/0253/15. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.