title: GABA depolarization is required for experience-dependent synapse unsilencing in adult-born neurons.
abstract: Neural activity enhances adult neurogenesis, enabling experience to influence the construction of new circuits. GABAA receptor-mediated depolarization of newborn neurons in the adult and developing brain promotes glutamatergic synaptic integration since chronic reduction of GABA depolarization impairs morphological maturation and formation of glutamatergic synapses. Here we demonstrate an acute role of GABA depolarization in glutamatergic synaptic integration. Using proopiomelanocortin enhanced-green fluorescent protein reporter mice, we identify a developmental stage when adult-generated neurons have glutamatergic synaptic transmission mediated solely by NMDA receptors (NMDARs), representing the initial silent synapses before AMPA receptor (AMPAR)-mediated functional transmission. We show that pairing synaptic stimulation with postsynaptic depolarization results in synapse unsilencing that requires NMDAR activation. GABA synaptic depolarization enables activation of NMDARs in the absence of AMPAR-mediated transmission and is required for synapse unsilencing induced by synaptic activity in vitro as well as a brief exposure to an enriched environment in vivo. The rapid appearance of AMPAR-mediated EPSCs and the lack of maturational changes show that GABA depolarization acutely allows NMDAR activation required for initial synapse unsilencing. Together, these results also reveal that adult-generated neurons in a critical period for survival use GABA signaling to rapidly initiate functional glutamate-mediated transmission in response to experience.
authors.affiliation: McKnight Brain Institute and Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Chancey
authors.forename: Elena W
authors.initials: EW
authors.lastname: Adlaf
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Sapp
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Pugh
authors.forename: Jacques I
authors.initials: JI
authors.lastname: Wadiche
authors.forename: Linda S
authors.initials: LS
authors.lastname: Overstreet-Wadiche
mesh_terms: D000818:Animals; D003423:Critical Period, Psychological; D004777:Environment; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D011333:Pro-Opiomelanocortin