title: Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines.
abstract: Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal.
authors.affiliation: Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States.|Program in Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, United States.
authors.forename: Sonia
authors.initials: S
authors.lastname: Afroz
authors.affiliation: Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States.|Program in Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, United States.
authors.forename: Julie
authors.initials: J
authors.lastname: Parato
authors.affiliation: Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States.|School of Biomedical Engineering, Tianjin Medical University, Tianjin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States.|The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, United States.
authors.forename: Sheryl Sue
authors.identifier: 0000-0003-4308-3267
authors.initials: SS
authors.lastname: Smith
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D051379:Mice; D009473:Neuronal Plasticity; D011627:Puberty; D017966:Pyramidal Cells / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A
keywords: GABA-A receptor; cell biology; delta; dendritic spine; hippocampus; mouse; neuroscience; puberty; synaptic pruning