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

TrkB Signaling Influences Gene Expression in Cortistatin-Expressing Interneurons.

Author information

1
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland 21205.
2
Department of Mental Health, Johns Hopkins University, Baltimore, Maryland 21205.
3
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
4
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
5
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
6
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland 21205 Keri.martinowich@libd.org.

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.

KEYWORDS:

ASD; BDNF-TrkB; Ribotag ; cortistatin; epilepsy; inhibitory interneurons

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