Requirement of TrkB for synapse elimination in developing cerebellar Purkinje cells

Brain Cell Biol. 2006 Feb;35(1):87-101. doi: 10.1007/s11068-006-9002-z. Epub 2007 Mar 1.

Abstract

The receptor tyrosine kinase TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), are critically important for growth, survival and activity-dependent synaptic strengthening in the central nervous system. These TrkB-mediated actions occur in a highly cell-type specific manner. Here we report that cerebellar Purkinje cells, which are richly endowed with TrkB receptors, develop a normal morphology in trkB-deficient mice. Thus, in contrast to other types of neurons, Purkinje cells do not need TrkB for dendritic growth and spine formation. Instead, we find a moderate delay in the maturation of GABAergic synapses and, more importantly, an abnormal multiple climbing fiber innervation in Purkinje cells in trkB-deficient mice. Thus, our results demonstrate an involvement of TrkB receptors in synapse elimination and reveal a new role for receptor tyrosine kinases in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Shape / physiology
  • Dendrites / physiology
  • Dendrites / ultrastructure
  • Dendritic Spines / physiology
  • Inhibitory Postsynaptic Potentials / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred ICR
  • Mice, Mutant Strains
  • Purkinje Cells / cytology*
  • Purkinje Cells / physiology*
  • Purkinje Cells / ultrastructure
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism*
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / physiology

Substances

  • Brain-Derived Neurotrophic Factor
  • gamma-Aminobutyric Acid
  • Receptor, trkB