Changes in the Morphology of Hypoglossal Motor Neurons in the Brainstem of Developing Rats

Abstract

The autonomic brainstem generates breathing rhythm by integrating inputs from chemosensors and mechanosensors in the viscera and coordinating descending outputs from higher structures in the central nervous system. Hypoglossal motoneurons (XII MNs) receive inputs from respiratory premotor neurons, important for maintaining airway patency. Previous studies in rodents report significant changes in breathing control during the first 3 weeks of life, with a sensitive period at 10 to 13 days postbirth (P10–P13) characterized by pronounced changes in neurotransmitters, excitation‐inhibition balance, and breathing physiology. However, age‐dependent morphological changes of XII MNs during the first 3 weeks postbirth and especially this sensitive period are under‐studied. Here, we comprehensively characterize and quantify the early morphological changes in rat XII MNs. We hypothesized that morphological changes in XII MNs correspond to the functionally defined sensitive period observed at postnatal day 10–13 (P10–P13). To test this hypothesis, we used an innovative contemporary statistical approach to analyze Golgi‐Cox stained XII MNs at nine postnatal ages between P1 and P21. Our findings reveal two subpopulations of XII MNs, which are dependent on age and morphological features. Soma size increased approximately 40% from P1 to P21, without changing shape. However, dendritic arborization increased in extent/distance and complexity. Dendritic branching of developing neurons significantly increased from P1 through P13, with the greatest increase at P10–P13 based on the Sholl method. Our detailed characterization of XII MN morphological development establishes a foundation for the study and elucidation of morphological changes caused by maternal and perinatal conditions. Anat Rec, 302:869–892, 2019. © 2018 Wiley Periodicals, Inc.

Size‐Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice

“…B,B′). Representative tracings were taken from NeuroExplorer (MBF Bioscience Inc.) and projected in the xy plane, in a manner similar to past studies (Bandaru et al, ; Klenowski et al, ; Williams et al, ).…”

Nitric oxide controls excitatory/inhibitory balance in the hypoglossal nucleus during early postnatal development

“…These observations argued on a presumably effect of l -NAME on somata size. At this point, it is interesting to remark that HMNs somata size experienced an increase of approximately 40% from P1 to P21 (Williams et al 2019a , b ). Thus, we hypothesized that l -NAME effects HMNs development by impacting on normal morphological changes, including adjustment in somata size, during postnatal development.…”

“…Interestingly, HMNs development impairment is related with sudden infant death syndrome (Konrat et al 1992 ; Lavezzi et al 2010 ) and obstructive sleep apnea (Remmers et al 1978 ). Normal anatomical maturation of HMNs (Cameron and Nunez-Abades 2000 ; Carrascal et al 2005 , 2015 ; Kanjhan et al 2016a , b ; Williams et al 2019a , b ) might be impaired by disruption of NOS transient expression in motor neurons. It can contribute to abnormal HN size, hypoplasia, and immaturity of HMNs found in sudden infant death syndrome (Konrat et al 1992 ; O’Kusky and Norman 1995 ; Ottaviani et al 2006 ; Lavezzi et al 2010 ).…”

“…Respiration is critical during development, throughout life, and must generate reliable, rhythmic motor output through an elaborate system of control (Williams et al 2019a ). However, the respiratory system is immature at birth and significant postnatal development occurs (Feldman et al 2013 ).…”

Size‐dependent dendritic maladaptations of hypoglossal motor neurons in SOD1G93A mice

“…While there is extensive literature on the development of dendrites and dendritic spines of hypoglossal MNs in rodents (Fogarty, Kanjhan, Bellingham, & Noakes, 2016;Fogarty, Kanjhan, Yanagawa, Noakes, & Bellingham, 2017;Kanjhan, Fogarty, Noakes, & Bellingham, 2015;Nunez-Abades & Cameron, 1995;Nunez-Abades, He, Barrionuevo, & Cameron, 1994;Powell, Gaddy, Xu, Fregosi, & Levine, 2016;Williams, Bellinger, & Wilson, 2018), very little has been done to correlate these morphologies with soma size or by motor unit type. Notably, multiple muscles innervated by hypoglossal MNs (genioglossus, hyoglossus, styloglossus, dorsal lingualis, ventral lingualis, verticalis lingualis and transversus lingualis) exhibit a range of muscle myosin heavy chain (MyHC) expression, including those of type I (MyHC SLOW ), type IIa (MyHC 2A ), type IIx (MyHC 2X ), and type IIb (MyHC 2B ) muscle fibers (Cullins & Connor, 2017;Kletzien, Russell, Leverson, & Connor, 2018), that comprise S, FR, FInt, and FF motor units, respectively (Schiaffino & Reggiani, 2011).…”