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

J Neurosci. 2015 Jan 14;35(2):643-7. doi: 10.1523/JNEUROSCI.3483-14.2015.

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.

Keywords: motor neuron disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Dendritic Spines / pathology*
  • Excitatory Postsynaptic Potentials*
  • Female
  • Male
  • Mice
  • Motor Cortex / metabolism
  • Motor Cortex / pathology
  • Motor Cortex / physiopathology*
  • Mutation
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • Pyramidal Cells / physiology*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1

Substances

  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1