Influence of Microinjection of Kynurenic acid into the Pre-Botzinger Complex on Swallowing in the Cat

Abstract

Recent evidence supports the involvement of the pre-BÖtzinger complex (pre-BOT) in spatiotemporal features of swallowing and swallowing-breathing coordination in mice. We hypothesized that pharmacological disruption of glutamate neurotransmission in this brainstem region would perturb the swallow motor pattern in anesthetized cats. Electromyograms (EMGs) of upper airway muscles were recorded in anesthetized, spontaneously breathing cats (n=5). Swallowing was induced by injection of 3 cc of water into the oropharynx. Multi-barrel micropipettes were employed to inject artificial cerebrospinal fluid or kynurenic acid (KYN; 50 mM, 44±3 nL per injection) bilaterally into the region of the pre-BOT. Microinjection sites were confirmed histologically by detection of fluorescent beads that were suspended in the microinjectate. Blocking glutamate-related neuronal excitation by bilateral microinjections of the nonspecific glutamate receptor antagonist kynurenic acid had no effect on the number of swallows induced by water injection (control 2.3±0.3; KYN 3.0±0.7; P<0.32). Swallow durations were significantly increased following microinjections of KYN from 691±54 ms to 812±81 ms (p<0.04). KYN significantly reduced the magnitudes of geniohyoid (control 97±3 % of median; Kyn 47±12% of control median, p<0.02), thyrohyoid (control 100±3% of median; KYN 69±8% of control median, p<0.01), and posterior cricoarytenoid (control 103±2% of median; KYN 74±8% of control median, p<0.04) muscle EMGs during swallowing. There was no significant effect of microinjection of KYN on the magnitudes of thyroartytenoid, mylohyoid, or thyropharyngeus electromyograms during swallowing. The results suggest that disruption of glutamate neurotransmission in the preBOT has preferential effects consistent with actions on motor drive to hypoglossal and ventrolateral motoneuron pools that participate in swallowing. Lengthening of swallow duration induced by KYN supports a role for the preBOT in modulating the excitability of the swallow oscillatory circuit. NIH HL163008; NIH HL 131716; HL 155721. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.