Cortistatin-expressing interneurons require TrkB signaling to suppress neural hyper-excitability
Autor: | Keri Martinowich, Yishan Mai, Brady J. Maher, Nicholas F. Hardy, Kristen R. Maynard, Julia L. Hill, Henry L. Hallock, Feng Yang, Robert J. Schloesser, Ming Ren, Dennisse V. Jimenez, Huei Ying Chen |
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Rok vydání: | 2018 |
Předmět: |
Histology
Interneuron Tropomyosin receptor kinase B Biology Hippocampal formation Hyperkinesis Inhibitory postsynaptic potential Epileptogenesis Synaptic Transmission 050105 experimental psychology Article Cortistatin (neuropeptide) 03 medical and health sciences 0302 clinical medicine Neurotrophic factors Interneurons Seizures medicine Animals 0501 psychology and cognitive sciences Mice Knockout Membrane Glycoproteins Behavior Animal General Neuroscience musculoskeletal neural and ocular physiology Brain-Derived Neurotrophic Factor 05 social sciences Neuropeptides Brain Excitatory Postsynaptic Potentials Neural Inhibition Protein-Tyrosine Kinases Brain Waves Mice Inbred C57BL medicine.anatomical_structure nervous system Excitatory postsynaptic potential Anatomy Sleep Neuroscience human activities 030217 neurology & neurosurgery Locomotion |
Zdroj: | Brain structurefunction. 224(1) |
ISSN: | 1863-2661 |
Popis: | 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. |
Databáze: | OpenAIRE |
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