GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling

Using two-color uncaging of glutamate and GABA in rat hippocampal slices, the authors show that appropriately timed activation of dendritic GABA A and glutamate receptors promotes spine shrinkage and elimination. These effects spread locally to adjacent spines, involve NMDA receptors and the recruitment of calcium nanodomains, and can compete with spine enlargement in an ADF/cofilin-dependent manner. 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 (