RT Journal Article
SR Electronic
T1 Motor Cortex Layer V Pyramidal Neurons Exhibit Dendritic Regression, Spine Loss, and Increased Synaptic Excitation in the Presymptomatic hSOD1<sup>G93A</sup> Mouse Model of Amyotrophic Lateral Sclerosis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 643
OP 647
DO 10.1523/JNEUROSCI.3483-14.2015
VO 35
IS 2
A1 Fogarty, Matthew J.
A1 Noakes, Peter G.
A1 Bellingham, Mark C.
YR 2015
UL http://www.jneurosci.org/content/35/2/643.abstract
AB 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 hSOD1G93A (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.