TrkB signaling regulates the developmental maturation of the somatosensory cortex

Mark E. Lush, Long Ma, Luis F. Parada

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

In the rodent central nervous system, the region of the cortex that responds to facial whisker stimulation is anatomically segregated into discrete regions called barrels. Each barrel is made up of layer IV cortical neurons that receive input from a separate whisker via innervation from the thalamus. It has been shown that neurotrophins play important roles in the development and plasticity of thalamic axon innervation into the visual and retrosplenial cortex. We now extend those findings to the investigation of the role of neurotrophin signaling in barrel cortex formation. We show that the neurotrophin receptor TrkB is expressed in the thalamus and cortex during the time of cortical innervation. The two TrkB ligands, brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), are expressed in the cortex at this time. Mice lacking TrkB demonstrate a developmental delay in the segregation of thalamic axons within barrels. In TrkB mutants, thalamic axons are abnormally uniform within layer IV of the cortex at postnatal day 4 compared to their control littermates, but show clear segregation into barrels 2 days later. This phenotype is recapitulated in BDNF mutant mice, but not in NT-4 mutant mice. These results demonstrate that BDNF is the sole TrkB ligand responsible for this phenotype. Analysis of conditional knockout mice that lack TrkB within the cortex, and not the thalamus, does not show a delay in thalamic axon segregation. These results indicate that TrkB expression in thalamic axons is important for the appropriate timing of barrel cortex development.

Original languageEnglish (US)
Pages (from-to)523-536
Number of pages14
JournalInternational Journal of Developmental Neuroscience
Volume23
Issue number6
DOIs
StatePublished - Oct 1 2005

Keywords

  • Barrel cortex
  • Brain derived neurotrophic factor
  • Neurotrophin-4
  • Neurotrophins

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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