title: The developmental switch in GABA polarity is delayed in fragile X mice.
abstract: Delays in synaptic and neuronal development in the cortex are key hallmarks of fragile X syndrome, a prevalent neurodevelopmental disorder that causes intellectual disability and sensory deficits and is the most common known cause of autism. Previous studies have demonstrated that the normal progression of plasticity and synaptic refinement during the critical period is altered in the cortex of fragile X mice. Although the disruptions in excitatory synapses are well documented in fragile X, there is less known about inhibitory neurotransmission during the critical period. GABAergic transmission plays a crucial trophic role in cortical development through its early depolarizing action. At the end of cortical critical period, response properties of GABA transform into their mature hyperpolarizing type due to developmental changes in intracellular chloride homeostasis. We found that the timing of the switch from depolarizing to hyperpolarizing GABA is delayed in the cortex of fragile X mice and there is a concurrent alteration in the expression of the neuronal chloride cotransporter NKCC1 that promotes the accumulation of intracellular chloride. Disruption of the trophic effects of GABA during cortical development could contribute to the altered trajectory of synaptic maturation in fragile X syndrome.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, Department of Pediatrics and Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, and Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois 60208.
authors.forename: Qionger
authors.initials: Q
authors.lastname: He
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nomura
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Anis
authors.initials: A
authors.lastname: Contractor
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003423:Critical Period, Psychological; D004195:Disease Models, Animal; D005600:Fragile X Syndrome / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D018408:Patch-Clamp Techniques; D060888:Real-Time Polymerase Chain Reaction; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D013003:Somatosensory Cortex / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D064506:Solute Carrier Family 12, Member 2; D005680:gamma-Aminobutyric Acid