{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:59:16Z","timestamp":1787687956396,"version":"build-2784847793"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Mesencephalic trigeminal neurons (MTNs) are the sole primary afferent neurons with cell bodies located within the central nervous system. MTNs convey proprioceptive inputs from masticatory muscles and periodontal ligaments, thereby contributing to the precise regulation of jaw\u2013oral motor functions. Through ionic mechanisms such as currents generated by the voltage-dependent sodium (Nav) channel isoform Nav1.6, hyperpolarization-activated currents, and persistent inward currents, MTNs generate sustained and burst firing that regulate masticatory rhythm and jaw-jerk reflex timing. Their activity is further modulated by neurotransmitters, including serotonin and norepinephrine, which provide flexibility in sensorimotor integration. Pathological conditions such as chronic stress and sodium channel dysfunction induce MTN hyperexcitability or irregular firing, contributing to bruxism, temporomandibular disorders, and feeding impairment in amyotrophic lateral sclerosis models. In addition, aging and tooth loss lead to Piezo2 downregulation and neuronal death, potentially resulting in masticatory dysfunction and cognitive decline. Recent findings suggest that interventions targeting vesicular glutamate transporter 1 projections, melanocortin 4 receptor signaling, and nitric oxide pathways represent novel therapeutic approaches. Taken together, MTNs have emerged as promising targets for treating conditions ranging from masticatory motor disorders to neurodegenerative diseases.<\/jats:p>","DOI":"10.3389\/fncel.2026.1752701","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:32:23Z","timestamp":1773120743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The mesencephalic trigeminal neuron: electrophysiological insights into function and dysfunction"],"prefix":"10.3389","volume":"20","author":[{"given":"Soju","family":"Seki","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, The University of Osaka","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kindai University, Faculty of Medicine","place":["Sakai, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, The University of Osaka","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.mehy.2014.11.005","article-title":"The mesencephalic nucleus of the trigeminal nerve and the SIDS","volume":"84","author":"Andrisani","year":"2015","journal-title":"Med. 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Physiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/0006-8993(89)91413-3","article-title":"Evidence for excitatory amino acid transmission between mesencephalic nucleus of V afferents and jaw-closer motoneurons in the guinea pig","volume":"477","author":"Chandler","year":"1989","journal-title":"Brain Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e0278205","DOI":"10.1371\/journal.pone.0278205","article-title":"Convergent innervations of mesencephalic trigeminal and vestibular nuclei neurons onto oculomotor and pre-oculomotor neurons-tract tracing and triple labeling in rats","volume":"17","author":"Chen","year":"2022","journal-title":"PLoS One"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1111\/ejn.12858","article-title":"Generation of resonance-dependent oscillation by mGluR-I activation switches single spiking to bursting in mesencephalic trigeminal sensory neurons","volume":"41","author":"Chung","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/0306-4522(90)90410-6","article-title":"Neurotransmitters and neuropeptides within the mesencephalic trigeminal nucleus of the rat: an immunohistochemical analysis","volume":"37","author":"Copray","year":"1990","journal-title":"Neuroscience"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"4341","DOI":"10.1523\/JNEUROSCI.6216-11.2012","article-title":"Synergy between electrical coupling and membrane properties promotes strong synchronization of neurons of the mesencephalic trigeminal nucleus","volume":"32","author":"Curti","year":"2012","journal-title":"J. Neurosci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1002\/aja.1001660406","article-title":"Contributions of placodal and neural crest cells to avian cranial peripheral ganglia","volume":"166","author":"D'Amico-Martel","year":"1983","journal-title":"Am. J. Anat."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/s0960-9822(07)00562-3","article-title":"Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase","volume":"8","author":"Danielian","year":"1998","journal-title":"Curr. Biol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e202313353","DOI":"10.1085\/jgp.202313353","article-title":"D-type K+ current rules the function of electrically coupled neurons in a species-specific fashion","volume":"155","author":"Dapino","year":"2023","journal-title":"J. Gen. Physiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1152\/jn.00029.2019","article-title":"Response to coincident inputs in electrically coupled primary afferents is heterogeneous and is enhanced by H-current (IH) modulation","volume":"122","author":"Davoine","year":"2019","journal-title":"J. Neurophysiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1152\/jn.1997.77.2.537","article-title":"Physiological and theoretical analysis of K+ currents controlling discharge in neonatal rat mesencephalic trigeminal neurons","volume":"77","author":"Del Negro","year":"1997","journal-title":"J. Neurophysiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1267\/ahc.20-00036","article-title":"The periodontium damage induces neuronal cell death in the trigeminal mesencephalic nucleus and neurodegeneration in the trigeminal motor nucleus in C57BL\/6J mice","volume":"54","author":"Dhar","year":"2021","journal-title":"Acta Histochem. Cytochem."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1152\/jn.00292.2007","article-title":"Sodium currents in mesencephalic trigeminal neurons from Nav1.6-null mice","volume":"98","author":"Enomoto","year":"2007","journal-title":"J. Neurophysiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.1523\/JNEUROSCI.5274-05.2006","article-title":"Participation of sodium currents in burst generation and control of membrane excitability in mesencephalic trigeminal neurons","volume":"26","author":"Enomoto","year":"2006","journal-title":"J. Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/jnr.24134","article-title":"Development of resurgent and persistent sodium currents in mesencephalic trigeminal neurons","volume":"96","author":"Enomoto","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/0925-4773(95)00435-1","article-title":"Brn-3.0 expression identifies early post-mitotic CNS neurons and sensory neural precursors","volume":"53","author":"Fedtsova","year":"1995","journal-title":"Mech. Dev."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"25923","DOI":"10.1038\/srep25923","article-title":"A critical role for Piezo2 channels in the mechanotransduction of mouse proprioceptive neurons","volume":"6","author":"Florez-Paz","year":"2016","journal-title":"Sci. Rep."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.3390\/nu13051642","article-title":"The mesencephalic trigeminal nucleus controls food intake and body weight via hindbrain POMC projections","volume":"13","author":"Fortin","year":"2021","journal-title":"Nutrients"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"112006","DOI":"10.1016\/j.isci.2025.112006","article-title":"Astrocyte-induced firing in primary afferent axons","volume":"28","author":"Gaudel","year":"2025","journal-title":"iScience"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3720","DOI":"10.1152\/jn.00515.2014","article-title":"Involvement of histaminergic inputs in the jaw-closing reflex arc","volume":"113","author":"Gemba","year":"2015","journal-title":"J. Neurophysiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e07477","DOI":"10.1016\/j.heliyon.2021.e07477","article-title":"The neurophysiological basis of bruxism","volume":"7","author":"Giovanni","year":"2021","journal-title":"Heliyon"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.3233\/JAD-200257","article-title":"Neurodegeneration of trigeminal mesencephalic neurons by the tooth loss triggers the progression of Alzheimer's disease in 3\u00d7Tg-AD model mice","volume":"76","author":"Goto","year":"2020","journal-title":"J. Alzheimer's Dis"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"26096","DOI":"10.1038\/srep26096","article-title":"Regulation of irregular neuronal firing by autaptic transmission","volume":"6","author":"Guo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2910","DOI":"10.1152\/jn.1997.77.6.2910","article-title":"Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro","volume":"77","author":"Hsiao","year":"1997","journal-title":"J. Neurophysiol."},{"key":"ref30","volume-title":"StatPearls [Internet]","author":"Huff","year":"2025"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1002\/dvdy.1197","article-title":"Early development of the mesencephalic trigeminal nucleus","volume":"222","author":"Hunter","year":"2001","journal-title":"Dev. Dyn."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/nn925","article-title":"Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons","volume":"5","author":"Inoue","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"C895","DOI":"10.1152\/ajpcell.00132.2016","article-title":"Defects in brainstem neurons associated with breathing and motor function in the Mecp2R168X\/Y mouse model of Rett syndrome","volume":"311","author":"Johnson","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3694","DOI":"10.1523\/JNEUROSCI.5641-03.2004","article-title":"Bidirectional interactions between h-channels and Na+-K+ pumps in mesencephalic trigeminal neurons","volume":"24","author":"Kang","year":"2004","journal-title":"J. Neurosci."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1425645","DOI":"10.3389\/fncel.2024.1425645","article-title":"Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer\u2019s disease","volume":"18","author":"Kang","year":"2024","journal-title":"Front. Cell. Neurosci."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0006-8993(99)01350-5","article-title":"Characteristics of the muscle spindle endings of the masticatory muscles in the rabbit under halothane anesthesia","volume":"833","author":"Kato","year":"1999","journal-title":"Brain Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3389\/fncel.2018.00113","article-title":"Inhibition of GluR current in microvilli of sensory neurons via Na+ microdomain coupling among GluR, HCN channel, and Na+\/K+ pump","volume":"12","author":"Kawasaki","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1469-7793.1998.00695.x","article-title":"Hyperpolarization-activated cationic currents (Ih) in neurones of the trigeminal mesencephalic nucleus of the rat","author":"Khakh","year":"1998","journal-title":"J. Physiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1113\/jphysiol.1997.sp021895","article-title":"ATP-gated cation channels (P2X purinoceptors) in trigeminal mesencephalic nucleus neurons of the rat","author":"Khakh","year":"1997","journal-title":"J. Physiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.3390\/nu15071651","article-title":"Analysis of feeding behavior characteristics in the cu\/Zn superoxide dismutase 1 (SOD1) SOD1G93A mice model for amyotrophic lateral sclerosis (ALS)","volume":"15","author":"Kitaoka","year":"2023","journal-title":"Nutrients"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3389\/fneur.2016.00044","article-title":"Changes in neuronal excitability by activated microglia: differential Na(+) current upregulation in pyramid-shaped and bipolar neurons by TNF-\u03b1 and IL-18","volume":"7","author":"Klapal","year":"2016","journal-title":"Front. Neurol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.archoralbio.2006.10.023","article-title":"A review of burst generation by trigeminal main sensory neurons","volume":"52","author":"Kolta","year":"2007","journal-title":"Arch. Oral Biol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-642-57176-3","article-title":"The mesencephalic trigeminal nucleus in the cat","volume":"153","author":"Lazarov","year":"2000","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/s0301-0082(01)00021-1","article-title":"Comparative analysis of the chemical neuroanatomy of the mammalian trigeminal ganglion and mesencephalic trigeminal nucleus","volume":"66","author":"Lazarov","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.brainresrev.2007.08.009","article-title":"Neurobiology of orofacial proprioception","volume":"56","author":"Lazarov","year":"2007","journal-title":"Brain Res. Rev."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41368-023-00246-z","article-title":"Transcriptional profiling of dental sensory and proprioceptive trigeminal neurons using single-cell RNA sequencing","volume":"15","author":"Lee","year":"2023","journal-title":"Int. J. Oral Sci."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/BF00193410","article-title":"A comparative physiological and morphological study of periodontal ligament mechanoreceptors represented in the trigeminal ganglion and the mesencephalic nucleus of the cat","volume":"190","author":"Linden","year":"1994","journal-title":"Anat. Embryol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"9705","DOI":"10.1523\/JNEUROSCI.1703-17.2017","article-title":"Action potential broadening in capsaicin-sensitive DRG neurons from frequency-dependent reduction of Kv3 current","volume":"37","author":"Liu","year":"2017","journal-title":"J. Neurosci."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"885569","DOI":"10.3389\/fncel.2022.885569","article-title":"Transcriptional alterations of mouse trigeminal ganglion neurons following orofacial inflammation revealed by single-cell analysis","volume":"16","author":"Liu","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3389\/fnmol.2019.00174","article-title":"Malocclusion generates anxiety-like behavior through a putative lateral habenula-mesencephalic trigeminal nucleus pathway","volume":"12","author":"Liu","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3389\/fnmol.2017.00304","article-title":"The molecular fingerprint of dorsal root and trigeminal ganglion neurons","volume":"10","author":"Lopes","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4172\/2325-9639.1000198","article-title":"How sleep bruxism and tension headaches affect the masseter inhibitory reflex","volume":"6","author":"Luco","year":"2017","journal-title":"J Sleep Disor Treat Care"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1159\/000118860","article-title":"A study of jaw reflexes of the awake cat during mastication and locomotion","volume":"25","author":"Lund","year":"1984","journal-title":"Brain Behav. Evol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/0006-8993(95)01439-x","article-title":"Morphological evidence for recurrent jaw-muscle spindle afferent feedback within the mesencephalic trigeminal nucleus","volume":"710","author":"Luo","year":"1996","journal-title":"Brain Res."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"7613","DOI":"10.1523\/JNEUROSCI.18-19-07613.1998","article-title":"Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons","volume":"18","author":"Magee","year":"1998","journal-title":"J. Neurosci."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1038\/s41398-024-03158-6","article-title":"Understanding novel neuromodulation pathways in tDCS: brain stem recordings in rats during trigeminal nerve direct current stimulation","volume":"14","author":"Majdi","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1152\/jn.1997.77.4.2227","article-title":"Modulation of jaw muscle spindle discharge during mastication in the rabbit","volume":"77","author":"Masuda","year":"1997","journal-title":"J. Neurophysiol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1016\/0306-4522(82)90256-1","article-title":"The cells of origin of the trigeminothalamic, trigeminospinal and trigeminocerebellar projections in the cat","volume":"7","author":"Matsushita","year":"1982","journal-title":"Neuroscience"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/BF00247900","article-title":"Sensory components facilitating jaw-closing muscle activities in the rabbit","volume":"76","author":"Morimoto","year":"1989","journal-title":"Exp. Brain Res."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/0003-9969(85)90154-2","article-title":"Characteristics of rhythmic jaw movements of the rabbit","volume":"30","author":"Morimoto","year":"1985","journal-title":"Arch. Oral Biol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/fncel.2018.00009","article-title":"Electrophysiological and morphological properties of \u03b1 and \u03b3 motoneurons in the rat trigeminal motor nucleus","volume":"12","author":"Nishimura","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1212\/wnl.32.5.563","article-title":"Afferent limb of the human jaw reflex: electrophysiologic and anatomic study","volume":"32","author":"Ongerboer de Visser","year":"1982","journal-title":"Neurology"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/s0028-3908(00)00108-8","article-title":"Properties of native P2X receptors in rat trigeminal mesencephalic nucleus neurones: lack of correlation with known, heterologously expressed P2X receptors","volume":"40","author":"Patel","year":"2001","journal-title":"Neuropharmacology"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1242\/dev.127.7.1349","article-title":"Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b","volume":"127","author":"Pattyn","year":"2000","journal-title":"Development"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3892\/br.2024.1747","article-title":"Neurobiology of bruxism: the impact of stress (review)","volume":"20","author":"Pavlou","year":"2024","journal-title":"Biomed Rep."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1073\/pnas.94.2.724","article-title":"Dendritic calcium conductances generate high-frequency oscillation in thalamocortical neurons","volume":"94","author":"Pedroarena","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1152\/jn.1999.82.3.1465","article-title":"Oscillatory membrane potential activity in the soma of a primary afferent neuron","volume":"82","author":"Pedroarena","year":"1999","journal-title":"J. Neurophysiol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.3390\/ijerph20021007","article-title":"Locus coeruleus dysfunction and trigeminal mesencephalic nucleus degeneration: a cue for periodontal infection mediated damage in Alzheimer\u2019s disease?","volume":"20","author":"Pisani","year":"2023","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/s0006-8993(02)03776-9","article-title":"Mesencephalic trigeminal neurons are innervated by nitric oxide synthase-containing fibers and respond to nitric oxide","volume":"960","author":"Pose","year":"2003","journal-title":"Brain Res."},{"key":"ref401","doi-asserted-by":"crossref","DOI":"10.5962\/bhl.title.48637","author":"Ram\u00f3n y Cajal","year":"1909","journal-title":"Histologie du Syst\u00e8me Nerveux de l\u2019Homme et des Vert\u00e9br\u00e9s"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1152\/jn.00176.2006","article-title":"Two opposing roles of 4-AP-sensitive K+ current in initiation and invasion of spikes in rat mesencephalic trigeminal neurons","volume":"96","author":"Saito","year":"2006","journal-title":"J. Neurophysiol."},{"key":"ref72","first-page":"51","article-title":"Homeostatic maintenance regulated by hypothalamic neuronal histamine","volume":"17","author":"Sakata","year":"1995","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1177\/153537020322801002","article-title":"Anti-obesity actions of mastication driven by histamine neurons in rats","volume":"228","author":"Sakata","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1113\/EP090769","article-title":"Hyperexcitability of muscle spindle afferents in jaw-closing muscles in experimental myalgia: evidence for large primary afferents involvement in chronic pain","volume":"109","author":"Sas","year":"2024","journal-title":"Exp. Physiol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"2967","DOI":"10.3390\/biomedicines11112967","article-title":"Characteristics of sensory neuron dysfunction in amyotrophic lateral sclerosis (ALS): potential for ALS therapy","volume":"11","author":"Seki","year":"2023","journal-title":"Biomedicine"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1002\/jnr.24583","article-title":"Neuropeptide Y modulates membrane excitability in neonatal rat mesencephalic V neurons","volume":"98","author":"Seki","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"8798","DOI":"10.1523\/JNEUROSCI.1214-19.2019","article-title":"Circuit-specific early impairment of proprioceptive sensory neurons in the sod1g93a mouse model for ALS","volume":"39","author":"Seki","year":"2019","journal-title":"J. Neurosci."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1111\/j.1365-2842.2006.01623.x","article-title":"Mechanisms of oral somatosensory and motor functions and their clinical correlates","volume":"33","author":"Sessle","year":"2006","journal-title":"J. Oral Rehabil."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0006-8993(90)91418-g","article-title":"Two types of jaw-muscle spindle afferents in the cat as demonstrated by intra-axonal staining with HRP","volume":"514","author":"Shigenaga","year":"1990","journal-title":"Brain Res."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/0006-8993(88)91206-1","article-title":"Morphology of single mesencephalic trigeminal neurons innervating masseter muscle of the cat","volume":"445","author":"Shigenaga","year":"1988","journal-title":"Brain Res."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1002\/cne.9026804035","article-title":"The central projection of masticatory afferent fibers to the trigeminal sensory nuclear complex and upper cervical spinal cord","volume":"268","author":"Shigenaga","year":"1988","journal-title":"J. Comp. Neurol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1146\/annurev.neuro.25.112701.142916","article-title":"Transcriptional codes and the control of neuronal identity","volume":"25","author":"Shirasaki","year":"2002","journal-title":"Annu. Rev. Neurosci."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1523\/jneurosci.10-01-00099.1990","article-title":"Noradrenergic modulation of the masseteric reflex in behaving cats II. Physiological studies","volume":"10","author":"Stafford","year":"1990","journal-title":"J Neurosci."},{"key":"ref84","first-page":"15","article-title":"Changes in the number of neurons in the mesencephalic and motor nuclei of the trigeminal nerve in the ageing mouse brain","volume":"151","author":"Sturrock","year":"1987","journal-title":"J. Anat."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1152\/jn.1948.11.5.445","article-title":"Anatomical considerations of monosynaptic reflex arcs","volume":"11","author":"Szent\u00e1gothai","year":"1948","journal-title":"J. Neurophysiol."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1002\/jnr.20822","article-title":"Serotonergic modulation of persistent sodium currents and membrane excitability via cyclic AMP-protein kinase a cascade in mesencephalic V neurons","volume":"83","author":"Tanaka","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"265","DOI":"10.2334\/josnusd.19-0141","article-title":"Orexins modulate membrane excitability in rat trigeminal motoneurons","volume":"62","author":"Tanaka","year":"2020","journal-title":"J. Oral Sci."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"135846","DOI":"10.1016\/j.neulet.2021.135846","article-title":"Persistent sodium conductance contributes to orexin-A-mediated modulation of membrane excitability in neonatal rat mesencephalic V neurons","volume":"753","author":"Tanaka","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.brainres.2019.05.013","article-title":"Serotonergic modulation of slow inward rectification in mesencephalic trigeminal neurons","volume":"1718","author":"Tanaka","year":"2019","journal-title":"Brain Res."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1152\/jn.00850.2002","article-title":"Development of inward rectification and control of membrane excitability in mesencephalic v neurons","volume":"89","author":"Tanaka","year":"2003","journal-title":"J. Neurophysiol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2010.07.051","article-title":"Immunolocalization of pro- and mature-brain derived neurotrophic factor (BDNF) and receptor TrkB in the human brainstem and hippocampus","volume":"1354","author":"Tang","year":"2010","journal-title":"Brain Res."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3389\/fncel.2018.00153","article-title":"Loss of axon bifurcation in mesencephalic trigeminal neurons impairs the maximal biting force in Npr2-deficient mice","volume":"12","author":"Ter-Avetisyan","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"841239","DOI":"10.3389\/fncel.2022.841239","article-title":"The nature of noradrenergic volume transmission from locus coeruleus to brainstem mesencephalic trigeminal sensory neurons","volume":"16","author":"Toyoda","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.neuroscience.2025.03.051","article-title":"Functional interaction of electrical coupling and H-current and its putative impact on inhibitory transmission","volume":"574","author":"Trigo","year":"2025","journal-title":"Neuroscience"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/(sici)1096-9861(19990628)409:2<237::aid-cne5>3.3.co;2-9","article-title":"NMDA receptor NR1 and NR2A\/B subunit expression in trigeminal neurons during early postnatal development","volume":"409","author":"Turman","year":"1999","journal-title":"J. Comp. Neurol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0006-8993(94)90257-7","article-title":"Immunohistochemical localization of glutamate and glutaminase in guinea pig trigeminal premotoneurons","volume":"634","author":"Turman","year":"1994","journal-title":"Brain Res."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1002\/syn.10059","article-title":"Differential NR2A and NR2B expression between trigeminal neurons during early postnatal development","volume":"44","author":"Turman","year":"2002","journal-title":"Synapse"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1002\/1096-9861(20001106)427:1<109::aid-cne7>3.0.co;2-t","article-title":"AMPA receptor subunit expression in trigeminal neurons during postnatal development","volume":"427","author":"Turman","year":"2000","journal-title":"J. Comp. Neurol."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1238950","DOI":"10.3389\/fendo.2023.1238950","article-title":"Editorial: endocrine consequences of sleep disorders","volume":"14","author":"Uchima Koecklin","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"5341","DOI":"10.1113\/JP284999","article-title":"Ih current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain","volume":"601","author":"Vasylyev","year":"2023","journal-title":"J. Physiol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"e1007154","DOI":"10.1371\/journal.pcbi.1007154","article-title":"Resurgent Na+ current offers noise modulation in bursting neurons","volume":"15","author":"Venugopal","year":"2019","journal-title":"PLoS Comput. Biol."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.1152\/jn.00279.2004","article-title":"Synaptic inputs to trigeminal primary afferent neurons cause firing and modulate intrinsic oscillatory activity","volume":"92","author":"Verdier","year":"2004","journal-title":"J. Neurophysiol."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00221-023-06746-y","article-title":"The ultrastructure of macaque mesencephalic trigeminal nucleus neurons","volume":"242","author":"Wang","year":"2023","journal-title":"Exp. Brain Res."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/0896-6273(89)90238-9","article-title":"Differential subcellular localization of the RI and RII forms of the alpha subunit of the sodium channel in rat central neurons","volume":"3","author":"Westenbroek","year":"1989","journal-title":"Neuron"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1038\/nn.4162","article-title":"Piezo2 is the principal mechanotransduction channel for proprioception","volume":"18","author":"Woo","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1152\/jn.90346.2008","article-title":"Coupling of L-type Ca2+ channels to Kv7\/KCNQ channels creates a novel, activity-dependent, homeostatic intrinsic plasticity","volume":"100","author":"Wu","year":"2005","journal-title":"J. Neurophysiol."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"2710","DOI":"10.1152\/jn.00636.2004","article-title":"Persistent sodium currents in mesencephalic v neurons participate in burst generation and control of membrane excitability","volume":"93","author":"Wu","year":"2005","journal-title":"J. Neurophysiol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.1523\/jneurosci.21-11-03729.2001","article-title":"Membrane resonance and subthreshold membrane oscillations in mesencephalic V neurons: participants in burst generation","volume":"21","author":"Wu","year":"2001","journal-title":"J. Neurosci."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1159\/000369822","article-title":"Electrophysiological features of neurons in the mesencephalic trigeminal nuclei","volume":"22","author":"Xing","year":"2014","journal-title":"Neurosignals"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"242","DOI":"10.2334\/josnusd.20-0566","article-title":"Membrane excitabilities in neonatal rat mesencephalic trigeminal neurons under dietary zinc deficiency","volume":"63","author":"Yamada","year":"2021","journal-title":"J. Oral Sci."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-981-32-9636-7_9","article-title":"Oligodendrocyte physiology modulating axonal excitability and nerve conduction","volume":"1190","author":"Yamazaki","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"177","DOI":"10.2334\/josnusd.16-0845","article-title":"Projection and synaptic connectivity of trigeminal mesencephalic nucleus neurons controlling jaw reflexes","volume":"59","author":"Yoshida","year":"2017","journal-title":"J. Oral Sci."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.neuron.2004.07.010","article-title":"Cell behaviors and genetic lineages of the mesencephalon and rhombomere 1","volume":"43","author":"Zervas","year":"2004","journal-title":"Neuron"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.brainres.2012.10.021","article-title":"Jaw muscle spindle afferents coordinate multiple orofacial motoneurons via common premotor neurons in rats: an electrophysiological and anatomical study","volume":"1489","author":"Zhang","year":"2012","journal-title":"Brain Res."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"841133","DOI":"10.3389\/fncel.2022.841133","article-title":"Activation of the mesencephalic trigeminal nucleus contributes to masseter hyperactivity induced by chronic restraint stress","volume":"16","author":"Zhao","year":"2022","journal-title":"Front. Cell. 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