Alterations in hypoglossal motor neurons due to GAD67 and VGAT deficiency in mice

Fogarty, Matthew J., Kanjhan, Refik, Yanagawa, Yuchio, Noakes, Peter G. and Bellingham, Mark C. (2017) Alterations in hypoglossal motor neurons due to GAD67 and VGAT deficiency in mice. Experimental Neurology, 289 117-127. doi:10.1016/j.expneurol.2016.12.004

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Author Fogarty, Matthew J.
Kanjhan, Refik
Yanagawa, Yuchio
Noakes, Peter G.
Bellingham, Mark C.
Title Alterations in hypoglossal motor neurons due to GAD67 and VGAT deficiency in mice
Journal name Experimental Neurology   Check publisher's open access policy
ISSN 1090-2430
Publication date 2017-03-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.expneurol.2016.12.004
Open Access Status File (Author Post-print)
Volume 289
Start page 117
End page 127
Total pages 11
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Abstract There is an emerging body of evidence that glycinergic and GABAergic synaptic inputs onto motor neurons (MNs) help regulate the final number of MNs and axonal muscle innervation patterns. Using mutant glutamate decarboxylase 67 (GAD67) and vesicular inhibitory amino acid transporter (VGAT) deficient mice, we describe the effect that deficiencies of presynaptic GABAergic and/or glycinergic release have on the post-synaptic somato-dendritic structure of motor neurons, and the development of excitatory and inhibitory synaptic inputs to MNs. We use whole-cell patch clamp recording of synaptic currents in E18.5 hypoglossal MNs from brainstem slices, combined with dye-filling of these recorded cells with Neurobiotin™, high-resolution confocal imaging and 3-dimensional reconstructions. Hypoglossal MNs from GAD67- and VGAT-deficient mice display decreased inhibitory neurotransmission and increased excitatory synaptic inputs. These changes are associated with increased dendritic arbor length, increased complexity of dendritic branching, and increased density of spiny processes. Our results show that presynaptic release of inhibitory amino acid neurotransmitters are potent regulators of hypoglossal MN morphology and key regulators of synaptic inputs during this critical developmental time point.
Keyword Brainstem
Motor neuron
Synaptic currents
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID LE100100074
Institutional Status UQ

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