Altered sensory processing and dendritic remodeling in hyperexcitable visual cortical networks

Brain Struct Funct. 2016 Jul;221(6):2919-36. doi: 10.1007/s00429-015-1080-1. Epub 2015 Jul 12.

Abstract

Epilepsy is characterized by impaired circuit function and a propensity for spontaneous seizures, but how plastic rearrangements within the epileptic focus trigger cortical dysfunction and hyperexcitability is only partly understood. Here we have examined alterations in sensory processing and the underlying biochemical and neuroanatomical changes in tetanus neurotoxin (TeNT)-induced focal epilepsy in mouse visual cortex. We documented persistent epileptiform electrographic discharges and upregulation of GABAergic markers at the completion of TeNT effects. We also found a significant remodeling of the dendritic arbors of pyramidal neurons, with increased dendritic length and branching, and overall reduction in spine density but significant preservation of mushroom, mature spines. Functionally, spontaneous neuronal discharge was increased, visual responses were less reliable, and electrophysiological and behavioural visual acuity was consistently impaired in TeNT-injected mice. These data demonstrate robust, long-term remodeling of both inhibitory and excitatory circuitry associated with specific disturbances of network function in neocortical epilepsy.

Keywords: Dendritic spines; Epilepsy; Spontaneous activity; Tetanus neurotoxin; Visual acuity; Visual cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendrites / pathology*
  • Dendrites / physiology
  • Epilepsies, Partial / chemically induced
  • Epilepsies, Partial / metabolism
  • Epilepsies, Partial / pathology*
  • Epilepsies, Partial / physiopathology*
  • Evoked Potentials, Visual*
  • GABAergic Neurons / metabolism
  • Metalloendopeptidases
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity*
  • Photic Stimulation
  • Pyramidal Cells / pathology
  • Pyramidal Cells / physiology
  • Tetanus Toxin
  • Up-Regulation
  • Vesicle-Associated Membrane Protein 2 / metabolism
  • Visual Acuity
  • Visual Cortex / metabolism
  • Visual Cortex / pathology*
  • Visual Cortex / physiopathology*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Tetanus Toxin
  • Vesicle-Associated Membrane Protein 2
  • vesicle-associated membrane protein 2, mouse
  • tetanospasmin
  • gamma-Aminobutyric Acid
  • Metalloendopeptidases