title: Genetic absence of the vesicular inhibitory amino acid transporter differentially regulates respiratory and locomotor motor neuron development.
abstract: During mid to late embryonic development (E13 to birth in mice), the neuromotor system is refined by reducing motor neuron (MN) numbers and establishing nascent synaptic connections onto and by MNs. Concurrently, the response to GABAergic and glycinergic synaptic activity switches from postsynaptic excitation to inhibition. Our previous studies on mutant mice lacking glycinergic transmission or deficient in GABA suggests that altered MN activity levels during this developmental period differentially regulates MN survival and muscle innervation for respiratory and non-respiratory motor pools. To determine if combined loss of GABAergic and glycinergic transmission plays a similar or exaggerated role, we quantified MN number and muscle innervation in two respiratory (hypoglossal and phrenic) and two locomotor (brachial and lumbar) motor pools, in mice lacking vesicular inhibitory amino acid transporter, which display absent or severely impaired GABAergic and glycinergic neurotransmission. For respiratory MNs, we observed significant decreases in MN number (-20 % hypoglossal and -36 % phrenic) and diaphragm axonal branching (-60 %). By contrast, for non-respiratory brachial and lumbar MNs, we observed increases in MN number (+62 % brachial and +84 % lumbar) and axonal branching for innervated muscles (+123 % latissimus dorsi for brachial and +61 % gluteal for lumbar). These results show that combined absence of GABAergic and glycinergic neurotransmission causes distinct regional changes in MN number and muscle innervation, which are dependent upon the motor function of the specific motor pool.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, QLD, 4072, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fogarty
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Obata
authors.forename: Mark C
authors.initials: MC
authors.lastname: Bellingham
authors.forename: Peter G
authors.initials: PG
authors.lastname: Noakes
mesh_terms: D000367:Age Factors; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000196:embryology; D002452:Cell Count; D002470:Cell Survival; D003964:Diaphragm / Q000294:innervation; D004622:Embryo, Mammalian; D005260:Female; D005998:Glycine / Q000378:metabolism; D008124:Locomotion / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009469:Neuromuscular Junction / Q000196:embryology / Q000235:genetics*; D011247:Pregnancy; D011950:Receptors, Cholinergic / Q000378:metabolism; D012119:Respiration / Q000235:genetics*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000172:deficiency* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011950:Receptors, Cholinergic; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D005680:gamma-Aminobutyric Acid; D005998:Glycine