TrkB Signaling Influences Gene Expression in Cortistatin-Expressing Interneurons

eNeuro. 2020 Feb 10;7(1):ENEURO.0310-19.2019. doi: 10.1523/ENEURO.0310-19.2019. Print 2020 Jan/Feb.


Brain-derived neurotrophic factor (BDNF) signals through its cognate receptor tropomyosin receptor kinase B (TrkB) to promote the function of several classes of inhibitory interneurons. We previously reported that loss of BDNF-TrkB signaling in cortistatin (Cort)-expressing interneurons leads to behavioral hyperactivity and spontaneous seizures in mice. We performed bulk RNA sequencing (RNA-seq) from the cortex of mice with disruption of BDNF-TrkB signaling in cortistatin interneurons, and identified differential expression of genes important for excitatory neuron function. Using translating ribosome affinity purification and RNA-seq, we define a molecular profile for Cort-expressing inhibitory neurons and subsequently compare the translatome of normal and TrkB-depleted Cort neurons, revealing alterations in calcium signaling and axon development. Several of the genes enriched in Cort neurons and differentially expressed in TrkB-depleted neurons are also implicated in autism and epilepsy. Our findings highlight TrkB-dependent molecular pathways as critical for the maturation of inhibitory interneurons and support the hypothesis that loss of BDNF signaling in Cort interneurons leads to altered excitatory/inhibitory balance.

Keywords: ASD; BDNF-TrkB; Ribotag; cortistatin; epilepsy; inhibitory interneurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Gene Expression
  • Interneurons*
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Neuropeptides*
  • Protein-Tyrosine Kinases
  • Receptor, trkB


  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Neuropeptides
  • cortistatin
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases
  • Receptor, trkB