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
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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