Maturation of "Neocortex Isole" in Vivo in Mice

J Neurosci. 2010 Jun 9;30(23):7928-39. doi: 10.1523/JNEUROSCI.6005-09.2010.

Abstract

How much neocortical development depends on connections remains elusive. Here, we show that Celsr3|Dlx mutant mice have no extrinsic neocortical connections yet survive to postnatal day 20, acquire a basic behavioral repertoire, and display spontaneous hyperactivity, with abnormal light/dark activity cycling. Except for hallmarks related to thalamic input, such as barrels in somatosensory cortex, cortical arealization and laminar maturation proceeded normally. However, the tangential extension of the mature cortex was diminished, with radial thickness less severely affected. Deep layer neurons were reduced in number, and their apical and basal dendritic arbors were blunted, with reduced synapse density. Interneurons reached the cortex, and their density was comparable with wild type. The excitability of mutant pyramidal neurons, measured in vitro in patch-clamp experiments in acute slices, was decreased. However, their firing activity in vivo was quite similar to the wild type, except for the presence of rapid firing exhaustion in some mutant neurons. Local field potential and electrocorticogram showed similar range of oscillations, albeit with higher frequency peaks and reduced left-right synchrony in the mutant. Thus, "protomap" formation, namely cortical lamination and arealization, proceed normally in absence of extrinsic connections, but survival of projection neurons and acquisition of mature morphological and some electrophysiological features depend on the establishment of normal cortical-subcortical relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Dendrites / physiology*
  • Electrophysiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Interneurons / physiology
  • Locomotion / physiology
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neocortex / growth & development*
  • Patch-Clamp Techniques
  • Pyramidal Cells / physiology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Somatosensory Cortex / growth & development*
  • Synapses / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Cadherins
  • Celsr3 protein, mouse
  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • Receptors, Cell Surface
  • Transcription Factors