GABA promotes the competitive selection of dendritic spines by controlling local Ca 2+ signaling

Abstract

Activity-dependent competition of synapses plays a key role in neural organization and is often promoted by GABA; however, its cellular bases are poorly understood. Excitatory synapses of cortical pyramidal neurons are formed on small protrusions known as dendritic spines, which exhibit structural plasticity. We used two-color uncaging of glutamate and GABA in rat hippocampal CA1 pyramidal neurons and found that spine shrinkage and elimination were markedly promoted by the activation of GABA A receptors shortly before action potentials. GABAergic inhibition suppressed bulk increases in cytosolic Ca 2+ concentrations, whereas it preserved the Ca 2+ nanodomains generated by NMDA-type receptors, both of which were necessary for spine shrinkage. Unlike spine enlargement, spine shrinkage spread to neighboring spines (<15 μm) and competed with their enlargement, and this process involved the actin-depolymerizing factor ADF/cofilin. Thus, GABAergic inhibition directly suppresses local dendritic Ca 2+ transients and strongly promotes the competitive selection of dendritic spines. © 2013 Nature America, Inc. All rights reserved.