Recent reports of slow tonic myosin heavy chain (MHCst) in human masticatory and laryngeal muscles suggest that MHCst may have a wider distribution in humans than previously thought. Because of the novelty of this finding, we sought to confirm the presence of MHCst in human masticatory and laryngeal muscles by reacting tissue from these muscles and controls from extraocular, intrafusal, cardiac, appendicular and developmental muscle with antibodies (Abs) ALD-58 and S46 considered highly specific for MHCst. At Ab dilutions producing minimal reaction to muscle fibers positive for MHCI, only extraocular, intrafusal and fetal tongue tissue reacted with Ab S46 had strong immunoreaction in an appreciable number of muscle fibers. In immunoblots Ab S46, but not Ab ALD-58, labeled adult extraocular muscles; no other muscles were labeled with either Ab. We conclude that, in humans, Ab S46 has greater specificity for MHCst than does Ab ALD-58. We suggest that reports of MHCst in human masticatory and laryngeal muscles reflect false-positive identification of MHCst due to cross-reactivity of Ab ALD-58 with another MHC isoform.

Tongue dysfunction is a hallmark of many human clinical disorders, yet we lack even a rudimentary understanding of tongue neural control. Here, the location and contractile properties of intrinsic longitudinal motor units (MUs) of the rat tongue body are described to provide a foundation for developing and testing theories of tongue motor control. One hundred and sixty-five MUs were studied by microelectrode penetration and stimulation of individual motor axons coursing in the terminal portion of the lateral (retrusor) branch of the hypoglossal nerve in the rat. Uniaxial MU force was recorded by a transducer attached to the protruded tongue tip, and MU location was estimated by electromyographic (EMG) electrodes implanted into the anterior, middle, and posterior portions of the tongue body. All MUs produced retrusive force. MU twitch force ranged from 2-129 mg (mean = 35 mg) and tetanic force ranged from 9-394 mg (mean = 95 mg). MUs reached maximal twitch force in 8-33 ms (mean = 15 ms) and were resistant to fatigue; following 2 min of stimulation, MUs (n = 11) produced 78-131% of initial force. EMG data were collected for 105 MUs. For 65 of these MUs, the EMG response was confined to a single electrode location: for 26 MUs to the anterior, 21 MUs to the middle, and 18 MUs to the posterior portion of the tongue. Of the remaining MUs, EMG responses were observed in two (38/40) or all three (2/40) tongue regions. These data provide the first contractile measures of identified intrinsic tongue body MUs and the first evidence that intrinsic longitudinal MUs are restricted to a portion of tongue length. Localization of MU territory suggests a role for intrinsic MU in the regional control of the mammalian tongue observed during feeding and speech.

The movements of the tongue in feeding and vocalization are enabled by a complex system of interdigitated muscle fibers in the tongue body. Because of this complexity, the detailed anatomical connections between individual intrinsic tongue muscles and corresponding motoneurons in the hypoglossal nucleus have not been described for any mammal. In this study we describe the distribution of retrogradely labeled neurons in the hypoglossal nucleus, following injections of wheat-germ agglutinin-horseradish peroxidase into different regions of the tongue of 21 cynomolgus monkeys. These experiments demonstrate a spatial organization of hypoglossal motoneurons that reflects the anatomical and functional organization of tongue body muscles: motoneurons innervating the transversus and verticalis muscles are located in medial hypoglossal nucleus regions, motoneurons innervating the genioglossus are located in intermediate hypoglossal nucleus regions, motoneurons innervating the hyoglossus and inferior longitudinalis are located in ventrolateral hypoglossal nucleus regions, and motoneurons innervating the styloglossus and superior longitudinalis are located in dorsolateral hypoglossal nucleus regions. Motoneurons innervating the suprahyoid muscle, the geniohyoid, are situated in a cell column separated ventrally from the main body of the hypoglossal nucleus. Motoneurons innervating the palatoglossus are located in the nucleus ambiguus and, possibly, in dorsolateral hypoglossal nucleus regions. Motoneurons of the medial divisions of the hypoglossal nucleus innervate tongue muscles that are oriented in planes transverse to the long axis of the tongue whereas motoneurons of the lateral divisions innervate tongue muscles that are oriented parallel to this axis. These results suggest that the segregation of motoneurons corresponds to the functional distinction between tongue protrusion and retrusion.

These data demonstrate differences in the relative percent of muscle fibre phenotypes in the macaque and human styloglossus but also demonstrate that all three phenotypes are present in both species. These data suggest a similar range of mechanical properties in styloglossus muscle fibres of the macaque and human.

Proper tongue function is essential for respiration and mastication, yet we lack basic information on the anatomical organization underlying human tongue movement. Here we use microdissection, acetylcholinesterase histochemistry, silver staining of nerves, alpha bungarotoxin binding and immunohistochemistry to describe muscle fiber architecture and motor endplate (MEP) distribution of the human superior longitudinalis muscle (SL). The human SL extends from tongue base to tongue tip and is composed of fiber bundles that range from 2.8 to 15.7 mm in length. Individual muscle fibers of the SL range from 1.2 to 17.3 mm in length (1.3–18.2% of muscle length). Seventy-one percent of SL fibers have blunt-blunt terminations; the remainder have blunt-taper terminations. Multiple MEPs are present along SL length and dual MEPs are present on some muscle fibers. These data demonstrate that the human SL is a muscle of ‘in-series’ design. We suggest that SL motor units are organized to innervate specific regions of the tongue body and that activation of SL motor units according to anteroposterior location is one strategy employed by the nervous system to control tongue shape and tongue movement.

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Key pointsr Millions of elderly individuals have dysphagia, a debilitating and life-threatening condition in which the ability to swallow is impaired.r Several muscles surround the three regions of the pharynx, which are essential for proper swallowing, yet the effects of ageing and disease on these muscles are not well understood.r We demonstrate that the fibre size of murine pharyngeal muscles is differentially affected by ageing and muscular dystrophy depending on their location within the pharynx.r Using a mouse model of an age-associated dysphagic disease (oculopharyngeal muscular dystrophy), we show that overexpression of wild-type polyadenylate binding nuclear protein 1 in muscle tissue prevents age-related dysphagia and age-related muscle atrophy of laryngopharyngeal muscles.r These results demonstrate that mice are an excellent model for studying mechanisms of ageing and disease on pharyngeal muscle physiology, and such studies could lead to new therapies for individuals with dysphagia.Abstract The inability to swallow, or dysphagia, is a debilitating and life-threatening condition that arises with ageing or disease. Dysphagia results from neurological or muscular impairment of one or more pharyngeal muscles, which function together to ensure proper swallowing and prevent the aspiration of food or liquid into the lungs. Little is known about the effects of age or disease on pharyngeal muscles as a group. Here we show ageing affected pharyngeal muscle growth and atrophy in wild-type mice depending on the particular muscle analysed. Furthermore, wild-type mice also developed dysphagia with ageing. Additionally, we studied pharyngeal muscles in a mouse model for oculopharyngeal muscular dystrophy, a dysphagic disease caused by a polyalanine expansion in the RNA binding protein, PABPN1. We examined pharyngeal muscles of mice overexpressing either wild-type A10 or mutant A17 PABPN1. Overexpression of mutant A17 PABPN1 differentially affected growth of the palatopharyngeus muscle dependent on its location within the pharynx. Interestingly, overexpression of wild-type A10 PABPN1 was protective against age-related muscle atrophy in the laryngopharynx and prevented the development of age-related dysphagia. These results demonstrate that pharyngeal muscles are differentially affected by both ageing and muscular dystrophy in a region-dependent manner. These studies lay important groundwork for understanding the molecular and cellular mechanisms that regulate pharyngeal muscle growth and atrophy, which may lead to novel therapies for individuals with dysphagia. Abbreviations A10-WT, wild-type A10.1 PABPN1 overexpression transgenic mouse; A17-MUT, mutant A17.1 PABPN1 overexpression transgenic mouse; FVB, Friend leukaemia virus B; H&E, haematoxylin and eosin; MHC, myosin heavy chains; OPMD, oculopharyngeal muscular dystrophy; PABPN1, polyadenylate binding nuclear protein 1; type I, slow twitch oxidative myofibre; type II, fast twitch glycolytic myofibre; WT, wild-type.

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