title: Cerebral Cortical Circuitry Formation Requires Functional Glycine Receptors.
abstract: The development of the cerebral cortex is a complex process that requires the generation, migration, and differentiation of neurons. Interfering with any of these steps can impair the establishment of connectivity and, hence, function of the adult brain. Neurotransmitter receptors have emerged as critical players to regulate these biological steps during brain maturation. Among them, α2 subunit-containing glycine receptors (GlyRs) regulate cortical neurogenesis and the present work demonstrates the long-term consequences of their genetic disruption on neuronal connectivity in the postnatal cerebral cortex. Our data indicate that somatosensory cortical neurons of Glra2 knockout mice (Glra2KO) have more dendritic branches with an overall increase in total spine number. These morphological defects correlate with a disruption of the excitation/inhibition balance, thereby increasing network excitability and enhancing susceptibility to epileptic seizures after pentylenetetrazol tail infusion. Taken together, our findings show that the loss of embryonic GlyRα2 ultimately impairs the formation of cortical circuits in the mature brain.
authors.affiliation: BIOMED Research Institute, Hasselt University, Hasselt 3500, Belgium.|GIGA-Neurosciences.|Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R).
authors.forename: Giovanni
authors.initials: G
authors.lastname: Morelli
authors.affiliation: Program in Neurosciences and Mental Health, SickKids Research Institute, The Hospital for Sick Children (SickKids), Toronto, ON, CanadaM5G 1X8.
authors.forename: Ariel
authors.initials: A
authors.lastname: Avila
authors.affiliation: BIOMED Research Institute, Hasselt University, Hasselt 3500, Belgium.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Ravanidis
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, C4N, Center for Neuroscience, Vrije Universiteit Brussel, 1090 Brussel, Belgium.
authors.forename: Najat
authors.initials: N
authors.lastname: Aourz
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Neve
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, C4N, Center for Neuroscience, Vrije Universiteit Brussel, 1090 Brussel, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.affiliation: Department of Pharmacology, UCL School of Pharmacy, London WC1N 1AX, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Harvey
authors.affiliation: BIOMED Research Institute, Hasselt University, Hasselt 3500, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rigo
authors.affiliation: GIGA-Neurosciences.|Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R).|Walloon Excellence in Lifesciences and Biotechnology (WELBIO), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: BIOMED Research Institute, Hasselt University, Hasselt 3500, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Brône
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010433:Pentylenetetrazole; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: C501173:Glra2 protein, mouse; D018009:Receptors, Glycine; D010433:Pentylenetetrazole
keywords: cerebral cortex; development; drug-induced epilepsy; glycine receptor; neuronal connectivity