Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex

Cereb Cortex. 2016 Feb;26(2):820-37. doi: 10.1093/cercor/bhv257. Epub 2015 Nov 11.

Abstract

Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory "barrel" cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position.

Keywords: c-fos; cortical layers; optogenetics; reelin; tracing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Action Potentials / physiology
  • Animals
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism
  • Gene Expression Regulation / genetics
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Neurologic Mutants
  • Mice, Transgenic
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Nerve Net / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / physiology*
  • Neurons / classification
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RGS Proteins / genetics
  • RGS Proteins / metabolism
  • Reelin Protein
  • Somatosensory Cortex / cytology*
  • Somatosensory Cortex / metabolism
  • Somatosensory Cortex / physiology*
  • Thalamus / physiology*
  • Vibrissae / physiology*

Substances

  • Epithelial Sodium Channels
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-fos
  • RGS Proteins
  • Reelin Protein
  • Scnn1a protein, mouse
  • Nerve Growth Factor
  • Reln protein, mouse