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Reelin signaling modulates GABA B receptor function in the neocortex
Author(s) -
Hamad Mohammad I. K.,
Jbara Abdalrahim,
Rabaya Obada,
Petrova Petya,
Daoud Solieman,
Melliti Nesrine,
Meseke Maurice,
Lutz David,
PetraschParwez Elisabeth,
Schwitalla Jan Claudius,
Mark Melanie D.,
Herlitze Stefan,
Reiss Gebhard,
Herz Joachim,
Förster Eckart
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14990
Subject(s) - neocortex , reelin , neuroscience , function (biology) , receptor , biology , microbiology and biotechnology , biochemistry
Reelin is a protein that is best known for its role in controlling neuronal layer formation in the developing cortex. Here, we studied its role for post-natal cortical network function, which is poorly explored. To preclude early cortical migration defects caused by Reelin deficiency, we used a conditional Reelin knock-out (Reln cKO ) mouse, and induced Reelin deficiency post-natally. Induced Reelin deficiency caused hyperexcitability of the neocortical network in vitro and ex vivo. Blocking Reelin binding to its receptors ApoER2 and VLDLR resulted in a similar effect. Hyperexcitability in Reln cKO organotypic slice cultures could be rescued by co-culture with wild-type organotypic slice cultures. Moreover, the GABA B receptor (GABA B R) agonist baclofen failed to activate and the antagonist CGP35348 failed to block GABA B Rs in Reln cKO mice. Immunolabeling of Reln cKO cortical slices revealed a reduction in GABA B R1 and GABA B R2 surface expression at the plasma membrane and western blot of Reln cKO cortical tissue revealed decreased phosphorylation of the GABA B R2 subunit at serine 892 and increased phosphorylation at serine 783, reflecting receptor deactivation and proteolysis. These data show a role of Reelin in controlling early network activity, by modulating GABA B R function. Cover Image for this issue: https://doi.org/10.1111/jnc.15054.