Direct and Collateral Alterations of Functional Cortical Circuits in a Rat Model of Subcortical Band Heterotopia

Cereb Cortex. 2019 Sep 13;29(10):4253-4262. doi: 10.1093/cercor/bhy307.

Abstract

Subcortical band heterotopia (SBH), also known as double-cortex syndrome, is a neuronal migration disorder characterized by an accumulation of neurons in a heterotopic band below the normotopic cortex. The majority of patients with SBH have mild to moderate intellectual disability and intractable epilepsy. However, it is still not clear how cortical networks are organized in SBH patients and how this abnormal organization contributes to improper brain function. In this study, cortical networks were investigated in the barrel cortex in an animal model of SBH induced by in utero knockdown of Dcx, main causative gene of this condition in human patients. When the SBH was localized below the Barrel Field (BF), layer (L) four projection to correctly positioned L2/3 pyramidal cells was weakened due to lower connectivity. Conversely, when the SBH was below an adjacent cortical region, the excitatory L4 to L2/3 projection was stronger due to increased L4 neuron excitability, synaptic strength and excitation/inhibition ratio of L4 to L2/3 connection. We propose that these developmental alterations contribute to the spectrum of clinical dysfunctions reported in patients with SBH.

Keywords: barrel field; cortical connectivity; electrophysiology; excitability. L4 inputs; subcortical band heterotopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Classical Lissencephalies and Subcortical Band Heterotopias / physiopathology*
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Gene Knockdown Techniques
  • Membrane Potentials
  • Microtubule-Associated Proteins / genetics
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Rats, Wistar
  • Somatosensory Cortex / pathology
  • Somatosensory Cortex / physiopathology*
  • Synapses / physiology*

Substances

  • DCX protein, human
  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides