title: Motor cortex layer V pyramidal neurons exhibit dendritic regression, spine loss, and increased synaptic excitation in the presymptomatic hSOD1(G93A) mouse model of amyotrophic lateral sclerosis.
abstract: Motor cortex layer V pyramidal neurons (LVPNs) regulate voluntary control of motor output and selectively degenerate (along with lower motor neurons) in amyotrophic lateral sclerosis. Using dye-filling and whole-cell patch clamping in brain slices, together with high-resolution spinning disk confocal z-stack mosaics, we characterized the earliest presymptomatic cortical LVPN morphologic and electrophysiological perturbations in hSOD1(G93A) (SOD1) mice to date. Apical dendritic regression occurred from postnatal day (P) 28, dendritic spine loss from P21, and increased EPSC frequency from P21 in SOD1 LVPNs. These findings demonstrate extensive early changes in motor cortex of the SOD1 mouse model, which thus recapitulates clinically relevant cortical pathophysiology more faithfully than previously thought.
authors.affiliation: School of Biomedical Sciences.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fogarty
authors.affiliation: School of Biomedical Sciences, Queensland Brain Institute, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Noakes
authors.affiliation: School of Biomedical Sciences, mark.bellingham@uq.edu.au.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Bellingham
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D049229:Dendritic Spines / Q000473:pathology*; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D008297:Male; D051379:Mice; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: motor neuron disease