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Pitman, M. J.

Publications and source records attributed to Pitman, M. J..

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The Expression of Vesicular Glutamate Transporter 1 (VGLUT1) in the Rat Larynx and Implications for Laryngeal Proprioception

Proprioception plays a crucial role in laryngeal function. Further, dysfunctional proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia and vocal fold paresis. Despite this, the physiology of laryngeal proprioception is not well-understood. Controversy remains over whether canonical proprioceptive organs, like muscle spindles (MS) even exist in the intrinsic laryngeal muscles (ILM). Vesicular Glutamate Transporter 1 (VGLUT1) expression has been described in the sensory afferents of MS. This studys primary aim is to determine whether the ILM contain MS using VGLUT1. This is a novel approach, as prior studies have relied on morphology and myosin composition to study this question. Secondarily, we describe the pattern of VGLUT1 expression in the rat larynx, Larynges of 62 Sprague-Dawley rats distributed across 5 age groups (P3, P8, P11, P14-15, and adult), were sectioned and immunostained for VGLUT1 and beta-tubulin III. Other markers (S46, GNAT3, PLC{beta}2, S100b, CGRP) were used to further characterize identified afferent innervation. Of 62 rats, MS were identified in the lateral thyroarytenoid muscles of just three P8 rats, and no golgi tendon organs (GTO) were seen. VGLUT1-positive intramuscular receptor-like entities were observed ILM, and VGLUT1-positive nerve endings were observed in the laryngeal mucosa, concentrated around the arytenoid cartilage. Employing VGLUT1 immunostaining, this study shows that rat intrinsic laryngeal muscles rarely express MS and do not express GTO. This leaves open the possibility that the larynx exhibits a unique proprioceptive apparatus. VGLUT1-positive intramuscular and mucosal structures provide candidates for an alternative system. Further defining the role of these sensory organs will increase our understanding of vocal fold function and ultimately lead to better treatment of vocal fold disorders. KEY POINTSO_LIDysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, and vocal fold paresis. Unlike proprioception of skeletal muscles, proprioception of the intrinsic laryngeal muscles is poorly understood. C_LIO_LIIn the present study we demonstrate that canonical proprioceptive organs (muscles spindles and Golgi tendon organs) are rarely expressed in the rat larynx, by studying the expression pattern of VGLUT1. C_LIO_LIWe also demonstrate the presence of other sensory innervation and structures which may contribute to an alternative proprioceptive circuitry, which requires further study. C_LI

neuroscience↗

Expression of GDNF Receptors Within Nucleus Ambiguus During Rat Development

ObjectiveUpregulation of GDNF and its receptors is observed during laryngeal reinnervation after nerve injury. In contrast, little is known regarding the expression of GDNF receptors in the formation of the nucleus ambiguus (NA) and its innervation of the larynx during embryogenesis. Differences may suggest therapeutic targets after nerve injury. Study DesignLaboratory experiment. MethodsRat brainstems at E14, E16, E18, E20, adult (4 animals/timepoint) were sectioned and stained for GDNF receptors: GFR-1, GFR-2, GFR-3, and Ret. Islet1 and ChAT were used as markers for motoneuron cell bodies. Sections were observed using Zeiss Axio Imager M2 Microscope and quantified using Image J. ResultsExpression of all four GDNF receptors was identified within the nucleus ambiguus, as well as hypoglossal and facial nuclei of the adult rat brainstem. During rat development, GFR-3 and Ret exhibited upregulation within the nucleus ambiguus at E14 whereas GFR-1 began showing upregulation at E20. GFR-2 exhibited no upregulation at embryonic timepoints. Conclusion: Upregulation of the GDNF receptors within the nucleus ambiguus occur after laryngeal muscles innervation during development and may associated with maturation and maintenance of the neuromuscular synapses of the larynx before and after birth. No differences among ambiguus, hypoglossal, and facial nuclei was observed.

neuroscience↗