Rbfox1 up-regulation impairs BDNF-dependent hippocampal LTP by dysregulating TrkB isoform expression levels

Elife. 2019 Aug 20:8:e49673. doi: 10.7554/eLife.49673.


Brain-derived neurotrophic factor (BDNF) is a potent modulator of brain synaptic plasticity. Signaling defects caused by dysregulation of its Ntrk2 (TrkB) kinase (TrkB.FL) and truncated receptors (TrkB.T1) have been linked to the pathophysiology of several neurological and neurodegenerative disorders. We found that upregulation of Rbfox1, an RNA binding protein associated with intellectual disability, epilepsy and autism, increases selectively hippocampal TrkB.T1 isoform expression. Physiologically, increased Rbfox1 impairs BDNF-dependent LTP which can be rescued by genetically restoring TrkB.T1 levels. RNA-seq analysis of hippocampi with upregulation of Rbfox1 in conjunction with the specific increase of TrkB.T1 isoform expression also shows that the genes affected by Rbfox1 gain of function are surprisingly different from those influenced by Rbfox1 deletion. These findings not only identify TrkB as a major target of Rbfox1 pathophysiology but also suggest that gain or loss of function of Rbfox1 regulate different genetic landscapes.

Keywords: RNA regulation; RbFox; TrkB; mouse; neuroscience; neurotrophins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Gene Expression Profiling
  • Hippocampus / physiology*
  • Long-Term Potentiation*
  • Membrane Glycoproteins / biosynthesis*
  • Mice
  • Protein Isoforms / biosynthesis
  • Protein-Tyrosine Kinases / biosynthesis*
  • RNA Splicing Factors / biosynthesis*
  • Sequence Analysis, RNA
  • Up-Regulation*


  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Protein Isoforms
  • RNA Splicing Factors
  • Rbfox1 protein, mouse
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases

Associated data

  • GEO/GSE136253
  • GEO/GSE71468