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Endogenous truncated TrkB.T1 receptor regulates neuronal complexity and TrkB kinase receptor function in vivo.

Pathological or in vitro overexpression of the truncated TrkB (TrkB.T1) receptor inhibits signaling through the full-length TrkB (TrkB.FL) tyrosine kinase receptor. However, to date, the role of endogenous TrkB.T1 is still unknown. By studying mice lacking the truncated TrkB.T1 isoform but retaining normal spatiotemporal expression of TrkB.FL, we have analyzed TrkB.T1-specific physiological functions and its effect on endogenous TrkB kinase signaling in vivo. We found that TrkB.T1-deficient mice develop normally but show increased anxiety in association with morphological abnormalities in the length and complexity of neurites of neurons in the basolateral amygdala. However, no behavioral abnormalities were detected in hippocampal-dependent memory tasks, which correlated with lack of any obvious hippocampal morphological deficits or alterations in basal synaptic transmission and long-term potentiation. In vivo reduction of TrkB signaling by removal of one BDNF allele could be partially rescued by TrkB.T1 deletion, which was revealed by an amelioration of the enhanced aggression and weight gain associated with BDNF haploinsufficiency. Our results suggest that, at the physiological level, TrkB.T1 receptors are important regulators of TrkB.FL signaling in vivo. Moreover, TrkB.T1 selectively affects dendrite complexity of certain neuronal populations.

Pubmed ID: 19158294 RIS Download

Mesh terms: Animals | Body Weight | Brain | Brain-Derived Neurotrophic Factor | Conditioning (Psychology) | Exploratory Behavior | Fear | Hippocampus | In Vitro Techniques | Maze Learning | Mice | Mice, Inbred C57BL | Mice, Knockout | Mutation | Neurons | Receptor, trkB | Silver Staining

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Associated grants

  • Agency: Intramural NIH HHS, Id: Z99 CA999999
  • Agency: Intramural NIH HHS, Id: Z01 BC010390-08
  • Agency: NINDS NIH HHS, Id: R01 NS052819
  • Agency: NIMH NIH HHS, Id: MH060478
  • Agency: NINR NIH HHS, Id: R01 NR010207-03
  • Agency: NINR NIH HHS, Id: R01 NR010207
  • Agency: NINDS NIH HHS, Id: NS052819
  • Agency: NIMH NIH HHS, Id: R25 MH060478

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