Trkb signaling influences gene expression in cortistatin-expressing interneurons

Kristen R. Maynard, Alisha Kardian, Julia L. Hill, Yishan Mai, Brianna Barry, Henry L. Hallock, Andrew E. Jaffe, Keri Martinowich

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numberENEURO.0310-19.2019
JournaleNeuro
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • ASD
  • BDNF-TrkB
  • Cortistatin
  • Epilepsy
  • Inhibitory interneurons
  • Ribotag

ASJC Scopus subject areas

  • Neuroscience(all)

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    Maynard, K. R., Kardian, A., Hill, J. L., Mai, Y., Barry, B., Hallock, H. L., Jaffe, A. E., & Martinowich, K. (2020). Trkb signaling influences gene expression in cortistatin-expressing interneurons. eNeuro, 7(1), [ENEURO.0310-19.2019]. https://doi.org/10.1523/ENEURO.0310-19.2019