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Brain Structure and Function
Published in: Brain Structure and Function 1/2019

01-01-2019 | Original Article

Cortistatin-expressing interneurons require TrkB signaling to suppress neural hyper-excitability

Authors: Julia L. Hill, Dennisse V. Jimenez, Yishan Mai, Ming Ren, Henry L. Hallock, Kristen R. Maynard, Huei-Ying Chen, Nicholas F. Hardy, Robert J. Schloesser, Brady J. Maher, Feng Yang, Keri Martinowich

Published in: Brain Structure and Function | Issue 1/2019

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Abstract

Signaling of brain-derived neurotrophic factor (BDNF) via tropomyosin receptor kinase B (TrkB) plays a critical role in the maturation of cortical inhibition and controls expression of inhibitory interneuron markers, including the neuropeptide cortistatin (CST). CST is expressed exclusively in a subset of cortical and hippocampal GABAergic interneurons, where it has anticonvulsant effects and controls sleep slow-wave activity (SWA). We hypothesized that CST-expressing interneurons play a critical role in regulating excitatory/inhibitory balance, and that BDNF, signaling through TrkB receptors on CST-expressing interneurons, is required for this function. Ablation of CST-expressing cells caused generalized seizures and premature death during early postnatal development, demonstrating a critical role for these cells in providing inhibition. Mice in which TrkB was selectively deleted from CST-expressing interneurons were hyperactive, slept less and developed spontaneous seizures. Frequencies of spontaneous excitatory post-synaptic currents (sEPSCs) on CST-expressing interneurons were attenuated in these mice. These data suggest that BDNF, signaling through TrkB receptors on CST-expressing cells, promotes excitatory drive onto these cells. Loss of excitatory drive onto CST-expressing cells that lack TrkB receptors may contribute to observed hyperexcitability and epileptogenesis.
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Metadata
Title
Cortistatin-expressing interneurons require TrkB signaling to suppress neural hyper-excitability
Authors
Julia L. Hill
Dennisse V. Jimenez
Yishan Mai
Ming Ren
Henry L. Hallock
Kristen R. Maynard
Huei-Ying Chen
Nicholas F. Hardy
Robert J. Schloesser
Brady J. Maher
Feng Yang
Keri Martinowich
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 1/2019
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-018-1783-1

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