Dissertations / Theses on the topic 'Genioglossus'

In most mammals, nutritive suckling is critical during the early neonatal period. The genioglossus (GG) muscle in rat plays an important role in protruding the tongue for efficient suckling. The purpose of this study was to examine the contractile properties and myosin heavy chain (MHC) phenotype of the GG following an early period of artificial rearing, which reduced nutritive suckling. Beginning at three days of age Sprague-Dawley rats were fed via implanted gastric cannula until postnatal day 14 (P14). At P14, artificially reared (AR) rat pups were either placed with a lactating dam until the end of the weaning period and allowed to mature until postnatal day 42 (P42), or anesthetized and prepared for physiological experimentation. GG contractile properties at P14 and P42 in AR and dam reared (DR) rats were obtained with a force transducer and digital recording system through stimulation of the medial branch of the hypoglossal nerve. Following physiological experimentation, muscle samples were removed and stored for MHC analysis. Comparisons were made between AR and DR groups at P14 and P42. At P14 maximum tetanic tension and fatigue index were lower in the AR group than the DR group and no differences were found in MHC distribution. By day 42, AR rats had a higher fatigue index that DR rats and DR rats had a higher percentage of MHCIIa than AR rats. The artificial rearing technique employed in this study was adequate to produce chronic changes in fatigue resistance and MHC distribution in GG muscle. GG muscle of premature human infants requiring early artificial feedings may develop similar changes in their contractile characteristics and MHC phenotype.

We know very little about how muscles and motor units in one region of the upper airway are impacted by adjustments in an adjacent airway region. In this case, the focus is on regulation of the expiratory airstream by the larynx and how changes in laryngeal aperture impact muscle motor unit activities downstream in the pharynx. We selected sound production as a framework for study as it requires (i) sustained expiratory airflow, (ii) laryngeal airway regulation for production of whisper and voice, and (iii) pharyngeal airway regulation for production of different vowel sounds. We used these features as the means of manipulating expiratory airflow, pharyngeal, and laryngeal airway opening to compare the effect of each on the activation of genioglossus (GG) muscle motor units in the pharynx. We show that some GG muscle motor units (a) discharge stably on expiration associated with production of vowel sounds, (b) are exquisitely sensitive to subtle alterations in laryngeal airflow, and (c) discharge at higher firing rates in high flow vs. low flow conditions even when producing the same vowel sound. Our results reveal subtle changes in GG motor unit discharge rates that correlate with changes imposed at the larynx, and which may contribute to the regulation of the expiratory airstream.

Objetivo: O propósito deste estudo consiste em avaliar a relação entre Força de Língua e medidas do posicionamento do hioide em crianças com diagnóstico de SAOS. Casuística e Método: Foram selecionadas crianças entre 07 e 12 anos, de ambos os gêneros, com história de roncos, apneias noturnas e respiração bucal crônica. Todas as crianças tiveram SAOS confirmada pela presença dos sintomas e pela polissonografia e foram divididas em dois grupos: pré-operatório e pós-operatório (pacientes que tinham diagnóstico de SAOS antes da adenotonsilectomia, e foram reavaliados 12 meses depois. Ambos os grupos foram submetidos à avaliação de força de língua isométrica máxima (FLIM), aplicada na posição de ponta e dorso de língua, através do dinamômetro (kgf) e por meio da radiografia lateral foi realizada avaliação craniofacial e posicionamento do hioide. Resultados: Na regressão linear em pacientes pré- operatório a medida cefalometrica D vert. H apresentou forte e significativa (p= 0,0083) relação negativa com a força em ponta de língua. Já em dorso de língua antes da cirurgia não foi significativa, para nenhuma das variáveis. Nos pacientes pós-operatório a FLIM do dorso e ponta foram significativamente (p<0,0330 e p<0,0098 respectivamente) relacionadas à medida cefalométrica C3-H. A comparação de medidas cefalométricas entre os grupos pré e pósoperatórios e entre o subgrupo residual e curados, não tiveram diferença na altura do hioide (HYS, HYMP, D Vert.H) e na relação ântero-posterior do hioide (D Horiz.H, C3-H). Em relação a FLIM da musculatura extrínseca da língua ao se compararem a média e desvio padrão nos pacientes pré e pós-operatório, observou-se que houve diferença para as medidas de força de língua (p= 0,0016 para dorso e p=0,0041 para ponta) entre eles. Não houve diferença entre os sub-grupos residual e curados. Conclusão: No presente estudo podemos concluir que existe relação entre a força do musculo lingual e a posição do osso hiode em crianças com SAOS. Ou seja, aumento na força dos músculos dilatadores da faringe pode influenciar a altura do hioide em crianças com SAOS.
Objective: The purpose of this study is to assess the relation between Force of the Tongue and measures of hyoid\'s positioning in children diagnosed with OSAS. Casuistry and Method: Were selected children between 07 and 12 years, from both genders, with snoring history, nocturnal apnea and chronic mouth breathing. All the children had OSAS confirmed by the sympton\'s presence and by the polysomnography and were divided into two groups: preoperative and postoperative (pacients that had OSAS diagnosed before the adenotonsillectomy,and were revaluated 12 months after. Both groups were submitted to maximum isometric tongue force, applied in the tip and in the back of the tongue, through the dynamometer and through the lateral radiography was performed a craniofacial evaluation and hyoid positioning. Results: In preoperative patients on linear regression the cephalometric measure D. vert. H presented strong and significant (p= 0,0083) negative relation with the tip of the tongue force. Whereas the back of the tongue before the surgery was not significant, for none of the variables. In postoperative patients the maximum isometric tongue force from the back and from the tip were significantly (p<0,0330 e p<0,0098 respectively) related to the cephalometric measure C3-H. The comparison between the cephalometric measures between the preoperative and postoperative groups and between the residual sub group and the healed ones, did not have difference in the hyoid\'s height (HYS, HYMP, D Vert.H) and on the hyoid\'s anteroposterior relation (D Horiz.H, C3-H). In regards to the maximum isometric tongue force from the extrinsic tongue musculature when compared to the average and standard deviation in patients pre and post surgery, it was noticed that there was difference for the tongue force measures (p= 0,0016 for the back and p=0,0041 for the tip) between them. There was no difference between the sub groups residual and healed. Conclusion: In the present study we can conclude that there is relation between the force of the lingual muscle and hyoid bone\'s position in children with OSAS. In other words, an increase on the pharynx dilator muscles\' strength can influence the hyoid\'s height in children with OSAS.

To effect movement, the central nervous system must appropriately coordinate the activities of pools of motoneurons (MNs), the cells which control muscle fibers. Sources of neural drive are often distributed to many MNs of a pool, and thus can synchronize the activities of targeted MNs. In this thesis, synchronization among MNs is used to investigate the strength, temporal progression, and anatomical distribution of neural drive to the hypoglossal motor nucleus (HMN), which controls muscles of the tongue. The HMN is an ideal target for such an investigation because it processes a host of functionally diverse inputs, such as those related to breathing, speaking, and swallowing. Study 1 characterizes motor unit (MU) synchronization within and across bellies of the human genioglossus (GG) muscle when MUs are activated by cortical drive (during voluntary tongue protrusion) or by automatic, brainstem-mediated drive (during rest breathing). We show that voluntary tongue protrusion synchronizes MU spike timing and firing rates within but not across bellies of the GG, whereas during rest breathing, MU firing rates are moderately synchronized both within and across muscle bellies. Study 2 documents respiratory-related synchronization of MU activities in muscles of the tongue and respiratory pump using an anesthetized rat model. The results of this study indicate that upper airway and respiratory pump MN pools share a low frequency respiratory-related drive, but that higher frequency (>8 Hz) synchronization is strongest in MU pairs of the chest-wall. Finally, Study 3 examines the potential for GG multi-unit and single MU activities to be entrained by cortical input. We show that during voluntary tongue protrusion, cortical oscillations in the 15-40 Hz range weakly synchronize MU population activity, and that EEG oscillations in this range intermittently influence the spike timing of individual GG MUs. These studies are the first to characterize MU synchronization by different sources of neural input to the HMN and establish a broad foundation for further investigation of hypoglossal motor control.

The obstructive sleep apnea and hypopnea syndrome (OSAS) is characterized by repeated episodes of complete or partial interruption of the airflow as consequence of upper airway obstruction during sleep. Indications for the surgical treatment of OSAS, as well as the evidence on the efficacy and safety of the surgical techniques available merit further scientific scrutiny. Objective: To perform a systematic review on the efficacy of genioglossus advancement (GA) when compared to maxillomandibular advancement (MMA) for the treatment of patients with OSAS. Method: A systematic electronic search was conducted in the LILACS, PubMed and SciELO databases to identify studies involving patients undergoing MMA and GA for the treatment of OSAS. The guidelines presented by the PRISMA statement were followed. The eligible articles were subjectively evaluated regarding their methodological quality based on a checklist of the Critical Appraisal Skills Programme (CASP). A meta-analysis was carried out with the aid of RevMan. Results: The systematic literature search resulted in 889 records, of which 41 articles were examined for their content. After full text analysis, six studies were included in this review and allowed for inferences about the efficacy of surgical procedures at hand. Conclusion: GA showed lower treatment efficacy, as evidenced by the apnea-hypopnea index recorded by polysomnography. The results of the meta-analysis show that the MMA is superior to GA in the context of surgical treatments for OSAS.
A Síndrome da Apneia e Hipopneia Obstrutiva do Sono (SAHOS) caracteriza-se por repetidos episódios de interrupção completa ou parcial do fluxo de ar inspirado durante o sono em função da obstrução das vias aéreas superiores. Os critérios para a indicação de tratamento cirúrgico da SAHOS, bem como as evidências sobre a eficácia e segurança das técnicas cirúrgicas que impactam as vias aéreas superiores ainda merecem exploração científica adicional.Objetivo: Avaliar, por meio de uma revisão sistemática, a eficácia do avanço do músculo genioglosso (AMG) comparado ao avanço maxilo-mandibular (AMM) no tratamento de pacientes com SAHOS.Método:uma busca eletrônica sistemática foi realizada nas bases de dados LILACS, PubMed e SciELO com o intuito de identificar estudos com pacientes submetidos a cirurgia de avanço maxilo-mandibular e avanço do musculo genioglosso para o tratamento da SAHOS. A metodologia seguiu as diretrizes do PRISMA statement.Os artigos elegíveis foram avaliados subjetivamente quanto à qualidade metodológica com baseem um dos questionários do Critical Appraisal Skills Programme(CASP).Uma meta-análise dos artigos incluídos foi realizada com o auxílio do software RevMan.Resultados:A busca sistemática da literatura resultou em889 registros, dos quais 41 artigos foram examinados quanto a seu conteúdo. Depois da análise dos textos completos, seis estudos foram incluídos nesta revisão, permitindo inferências sobre a eficácia dos procedimentos cirúrgicos em questão.Conclusão:O avanço do músculo genioglosso demonstrou eficácia inferior à do avanço do músculo genioglosso, o que foi evidenciado por meio do índice de apneia hipopneia registrados através de polissonografias.Os resultados da meta-análise mostram que o AMM apresenta eficácia superior àquela doAMG no contexto do tratamento cirúrgico da SAHOS.
Lagarto, SE

This thesis addresses the organisation of drive to human upper airway and inspiratory pump muscles. The characterisation of single motor unit activity is important as the discharge frequency or timing of discharge of each motor unit directly reflects the output of single motoneurones. Thus, the firing properties of a population of motor units is indicative of the neural drive to the motoneurone pool. The experiments presented in Chapter 2 measured the recruitment time of five inspiratory pump muscles (diaphragm, scalene, second parasternal intercostal, and third and fifth dorsal external intercostal muscles) during normal quiet breathing and quantified the timing and magnitude of drive reaching each muscle. Chapter 3 examined the EMG activity of a major upper airway muscle (the genioglossus). The single motor units of the genioglossus display activity that can be grouped into six types based on its association or lack of association with respiration. The types of activity are termed: Inspiratory Phasic, Inspiratory Tonic, Expiratory Phasic, Expiratory Tonic, Tonic, and Tonic Other. A new method is presented in Chapter 4 to illustrate large amounts of data from single motor units recorded from respiratory muscles in a concise manner. This single figure displays for each motor unit, the recruitment time and firing frequency, the peak discharge frequency and its time, and the derecruitment time and its frequency. This method, termed the time-and-frequency plot, is used to demonstrate differences in behaviour between populations of diaphragm (Chapter 2) and genioglossus (Chapter 3) motoneurones. In Chapter 5, genioglossus activity during quiet breathing is compared between a group of patients with severe OSA and healthy control subjects. The distribution of central drive is identical between the OSA and control subjects with the same proportion of the six types of motor unit activity in both groups. However, there are alterations in the onset time of Inspiratory Phasic and Inspiratory Tonic motor units in OSA subjects and their peak discharge rates are also altered. Single motor unit action potentials in OSA subjects showed an increased area. This suggests the presence of neurogenic changes and may provide a pathophysiological explanation for the increased multiunit electromyographic activity reported in OSA subjects during wakefulness.

Introdução: A apneia do sono é condição prevalente e apresenta forte correlação com as principais causas de morbidade e mortalidade na sociedade ocidental. A perda do controle neuromotor proveniente de estágios mais profundos do sono está associada ao colapso faríngeo e a patogênese da apneia obstrutiva do sono (SAOS). A língua é implicada como principal protagonista na patogênese da obstrução das vias aéreas superiores (VAS) durante o sono. Não há farmacoterapia para SAOS. Novas tecnologias moleculares para controle neuronal através da inserção de um receptor de membrana geneticamente modificado, denominado Designer Receptor Exclusively Activated by Designer Drugs [DREADDs], o qual pode ser ativado por uma droga inicialmente inerte, de alta especificdade, clozapina-n-oxide (CNO). Objetivos: 1) Modificar geneticamente os neurônios motores do núcleo do hipoglosso utilizando-se de DREADDs, o qual permite regular sua atividade; 2) Analisar a atividade do músculo genioglosso sob administração de CNO; 3) Desenvolver abordagens para rastreamento dos músculos protrusores e retratores da língua por marcadores retrógrados, injecção de subunidade B de toxina colérica (CTB-AF) e do vírus de pseudoraiva (PRV) 267 transportando um gene repórter, nos músculos efetores. Métodos: Receptores muscarínicos mutados em um vetor adenoviral associado (AAV) foram infundidos no núcleo do hipoglosso de camundongos via injeção esterotáxica bilateral. Após quatro semanas, período para expressão fenotípica, foram comparadas a atividade eletromiográfica do músculo genioglosso (EMGGG) em resposta a administração de ligante (CNO) versus solução salina. Em um segundo grupo foram realizadas infusões com vírus controle e comparação da EMGGG pré e pós infusão de CNO. Para rastreamento neural a CTB-AF foi injetado nos músculos protusores e retratores da língua e para expressão de Cre o vírus PRV-267 foi injetado no músculo genioglosso. A expressão dessas substâncias no núcleo do hipoglosso foi avaliada através de microscopia de fluorescência. Resultados: Dos dezoito camundongos injetados com DREADDs, dezesseis foram transfectados pelo vetor de AAV. Em camundongos onde o núcleo motor do hipoglosso foi corretamente atingido a EMGGG apresentou importante aumento após a administração de CNO. Em contraste, a atividade do genioglosso não apresentou alteração após a administração de soro fisiológico. Em três camundongos onde a transfecção ultrapassou os limites do núcleo foi observado arritmia respiratória após infusão do ligante. Todos animais infundidos com vírus controle foram adequadamente transfectados mas não apresentaram alteração eletromiográfica após a infusão de CNO. Foram diferenciados no núcleo do hipoglosso os neurônios motores da musculatura retratora e protusora da língua. A expressão intranuclear da enzima Cre-recombinase foi identificada no núcleo hipoglosso. Conclusão: A utilização de métodos quimiogenéticos para ativar grupos selecionados de neurônios motores em áreas cerebrais específicas representa técnica promissora para o estudo do controle neuromotor das VAS. Estes resultados sugerem que a terapia transgênica pode ser eficaz no tratamento da SAOS além de uma vasta gama de patologias que resultam de perturbações no controle neural das VAS. Através da manipulação das fibras musculares efetoras na língua foi possível a identificação do seu respectivo neurônio motor no núcleo do hipoglosso e induzi-lo a sintetizar uma enzima específica (Cre-recombinase)
Introduction: Sleep Apnea is a prevalent condition and strongly correlates with the major causes of morbidity and mortality in Western Society. The loss of motor input from deeper sleep stages is associated with pharyngeal collapsibility and the pathogenesis of obstructive sleep apnea (OSA). The tongue plays a major role in the pathogenesis of upper airway (UA) obstruction during sleep. There is no pharmacotherapy for OSA. New molecular techniques allow to control neuronal function by inserting a genetically modified membrane receptor termed the Designer Receptor Exclusively Activated by Designer Drugs [DREADDs] which can be activated by a highly specific and otherwise pharmacologically inert drug clozapine-N-oxide (CNO) Objectives: 1) To genetically modify the hypoglossal nucleus motor neurons using DREADDs, which allows to regulate their activity; 2) To analyze the genioglossal activity upon administration of CNO; 3) to develop novel approaches to targeting tongue protruders and retractors by retrograde tracers, cholera toxin subunit B (CTB-AF) and pseudorabies virus (PRV) 267 injection carrying a reporter gene into the effector muscles. Methods: Mutated muscarinic receptors in an adenoviral associated vector (AAV) were delivered to the hypoglossal nucleus via stereotactically bilateral injection. Four weeks after adenoviral delivery (expression period), responses in genioglossal electromyography (EMGGG) activity to intraperitoneal administration of CNO ligand vs. Saline (control) were compared in mice. In a second group, control-virus was infused and genioglossus muscle EMGGG was compared before and after CNO infusion. For neuronal tracing CTB-AF was injected into the protrusor and retractor muscles of the tongue and for Cre induction PRV-267 virus was injected in the genioglossus muscle. Expression of these substances in the hypoglossal nucleus were evaluated by fluorescence histology. Results: Of eighteen DREADDs injected mice, sixteen were transfected with AAV vector. After CNO administration EMGGG activity increased in mice where the hypoglossal motor nucleus was correctly targeted. In contrast, genioglossal activity was not augmented following saline administration. In three mice where transfection surpassed the nucleus limits, breathing arrhythmia was observed following ligand infusion. All animals infused with control virus were adequately transfected but did not present electromyographic change following CNO infusion. The motor neurons of the rectractor and protrusor musculature of the tongue were well differentiated in the hypoglossal nucleus. Intranuclear expression of Cre recombinase enzyme was identified in the hypoglossal nucleus. Conclusion: Utilizing chemogenetic methods to activate motor neuron groups in selected brain areas show promise to UA neuromotor control, and suggest that transgenic therapy may be effective in treating OSA and a wide range of pathologies that result in disturbances of UA neural control. By manipulating the effector muscle fibers of the tongue, it was possible to identify its respective motor neuron in the hypoglossal nucleus and to induce synthesis of a specific enzyme (Cre recombinase)

In the thesis the author deals with the surgical technique of the genioglossus advancement and hyoid myotomy (GAHM) in the obstructive sleep apnoea syndrome (OSAS) therapy. He focuses in particular on methods used to widen the upper airway by surgical modification of facial bones. Following the definition of the research objective in Chapter 1 and the general introduction in Chapter 2, we can find in Chapter 3 the description and definition of OSAS as well as physiological, pathophysiological and epidemiological notes on sleep, ventilation in sleep and OSAS. In Chapter 4 the author recommends some new methods of examining the upper airway that can be applied in an ordinary dental surgery to predict the risk of development or occurrence of OSAS in some patients. Chapter 5 includes an overview of therapeutic options for OSAS and a detailed description of different GAHM techniques. In accordance with the research objectives and the methodology described in Chapter 6, the results in Chapter 7 show, for a large sample of examined patients, the dependence of obesity (as expressed by the BMI) on the severity of OSAS, along with some cephalometric values in which such dependence has not been published so far. Then the chapter documents a high success rate of GAHM treatment of OSAS in operated patients. This is so,...

The transitions to and from sleep are critical periods for the genioglossus (GG) muscle and for general respiratory activity. Multiunit recordings suggest that the GG is important for patency of the upper airway (UA) as well as being a model for the activity of all muscles in the UA region. Multiunit EMG recordings show phasic GG activity falling at sleep onset, before increasing as nREM sleep progresses. Airway patency, which is attributable to UA muscles, is compromised during sleep and airway occlusion can occur in susceptible individuals. Arousal from sleep leads to an increase in UA muscle activity with inspiratory multiunit recruitment of the GG known to occur. It is thought that arousals are involved in maintaining patency of the UA, with arousals hypothesised to be involved in reopening the airway following an apneic event in sleep disordered breathing (SDB) syndromes such as Obstructive Sleep Apnea (OSA), although an opposing view suggests that arousals are incidental, rather than essential, events. (For full abstract see document)

Obstructive sleep apnoea (OSA) is a common respiratory disorder characterised by repetitive periods of upper airway (UA) collapse during sleep. OSA is more common in males and the obese but the reasons why remain poorly understood. Abdominal obesity, particularly common in males, is likely to indirectly modulate the amount of tension (tracheal traction) exerted on the UA by the trachea and other intrathoracic structures, potentially leading to increased UA collapsibility. Other factors such as lung volume changes with obesity, altered drive to UA muscles and exaggerated arousal responses are also likely to contribute to UA instability. An investigation of these potential contributing factors forms the basis of this thesis. In the first study, the effect of external abdominal compression on UA collapsibility during sleep was investigated in a group of obese male OSA patients. A large pneumatic cuff wrapped around the abdomen was inflated to increase intra-abdominal pressure, aiming to produce an upward force on the diaphragm, designed to reduce axial tension on the UA. Abdominal compression increased end-expiratory gastric (PGA) and end-expiratory transdiaphragmatic (PDI) pressure by ~50% and produced a significant rise in UA collapsibility compared to the cuff deflated condition. These data support that increased intra-abdominal pressure has a negative effect on UA function during sleep. This effect may help explain why obesity is the leading risk factor for OSA and why OSA affects men more than women, given that abdominal obesity is particularly common in obese males. In the second study, differences in minimum expiratory (tonic) diaphragm activity during wakefulness were compared between 8 obese OSA patients and 8 healthyweight controls. Changes in tonic diaphragm activity and lung volume following sleep onset were also compared between the two groups. There was no evidence of increased tonic diaphragmatic activity during wakefulness in obese OSA patients to support significant diaphragmatic compensation for abdominal compressive effects of obesity. There were small decrements in lung volume following sleep onset in both groups (<70 ml), with significantly greater lung volume and diaphragmatic EMG decrements when sleep onsets were immediately followed by respiratory events. While lung volume decrements at sleep onset were relatively small, this does not discount that UA function is not more sensitive to effects of reduced lung volume in obese OSA patients. To more closely investigate the potential interactive effects of obesity on physiological variables likely influencing UA function, the third study investigated the temporal relationships between a comprehensive range of relevant physiological variables leading into and following the termination of obstructive apnoeas during sleep in 6 obese OSA patients. Prior to UA obstruction, diaphragm and genioglossus muscle activity decreased, while UA resistance increased. Lung volume and end-expiratory PGA and end-expiratory PDI also fell during this period, consistent with diaphragm ascent. There was a substantial increase in ventilation, muscle activity and lung volume immediately following the termination of obstructive events. Respiratory events and arousals occurred in close temporal proximity prior to and following obstructive apnoeas, supporting that cyclical respiratory events and arousals may both help to perpetuate further events. The results from this study support that there is a ‘global’ loss in respiratory drive to UA dilator and pump muscles precipitating obstructive respiratory events. The associated decreases in UA dilator muscle activity and lung volume may therefore both contribute to the propensity for the UA to obstruct. In summary, increased intra-abdominal pressure was shown to negatively impact UA airway collapsibility during sleep. A decrease in lung volume at sleep onset and prior to UA obstruction further support that lung volume decrement, coincident with a decline in overall respiratory drive, potentially contributes to the propensity for airway obstruction. Further studies are needed to elucidate the relative contribution of relatively small changes in lung volume versus changes in respiratory and UA muscle activity per se on UA patency in OSA patients.
Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2010

This thesis tested the hypothesis that ethanol suppresses respiratory muscle activity by effects at the central motor pool and/or by state-dependent regulation of motor activity via influences on sleep/arousal processes. Ten rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states, and genioglossus and diaphragm electrodes for respiratory recordings. Studies were performed following intraperitoneal injection of ethanol (1.25g/kg) or vehicle. The effects on genioglossus activity of ethanol (0.025-1M) or vehicle applied directly to the hypoglossal motor nucleus were also determined in sixteen isoflurane-anaesthetized rats. The results of these studies suggest that ethanol at physiologically relevant concentrations promoted sleep, and altered electroencephalogram and postural motor activities indicative of a sedating effect. The lack of effect on genioglossus activity with ethanol applied directly to the hypoglossal motor pool suggests that the suppression observed with systemic administration may be mediated via effects on state-dependent processes rather than direct effects at the motor pool per se.

The mouth, throat, and face contain numerous muscles that participate in a large variety of orofacial behaviors. The jaw and tongue can move independently, and thus require a high degree of coordination among the muscles that move them to prevent self-injury. However, different orofacial behaviors require distinct patterns of coordination between these muscles. The method through which motor control circuitry might coordinate this activity has yet to be determined. Electrophysiological, immunohistochemical, and retrograde tracing studies have attempted to identify populations of premotor neurons which directly send information to orofacial motoneurons in an effort to identify sources of coordination. Yet these studies have not provided a complete picture of the population of neurons which monosynaptically connect to jaw and tongue motoneurons. Additionally, while many of these studies have suggested that premotor neurons projecting to multiple motor pools may play a role in coordination of orofacial muscles, no clear functional roles for these neurons in the coordination of natural orofacial movements has been identified.

In this dissertation, I took advantage of the recently developed monosynaptic rabies virus to trace the premotor circuits for the jaw-closing masseter muscle and tongue-protruding genioglossus muscle in the neonatal mouse, uncovering novel premotor inputs in the brainstem. Furthermore, these studies identified a set of neurons which form boutons onto motor neurons in multiple motor pools, providing a premotor substrate for orofacial coordination. I then combined a retrogradely traveling lentivirus with a split-intein mediated split-Cre recombinase system to isolate and manipulate a population of neurons which project to both left and right jaw-closing motor nuclei. I found that these bilaterally projecting neurons also innervate multiple other orofacial motor nuclei, premotor regions, and midbrain regions implicated in motor control. I anatomically and physiologically characterized these neurons and used optogenetic and chemicogenetic approaches to assess their role in natural jaw-closing behavior, specifically with reference to bilateral masseter muscle electromyogram (EMG) activity. These studies identified a population of bilaterally projecting neurons in the supratrigeminal nucleus as essential for maintenance of an appropriate level of masseter activation during natural chewing behavior in the freely moving mouse. Moreover, these studies uncovered two distinct roles of supratrigeminal bilaterally projecting neurons in bilaterally synchronized activation of masseter muscles, and active balancing of bilateral masseter muscle tone against an excitatory input. Together, these studies identify neurons which project to multiple motor nuclei as a mechanism by which the brain coordinates orofacial muscles during natural behavior.

Dissertation