Journal
NATURE NEUROSCIENCE
Volume 16, Issue 10, Pages 1409-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3496
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [21000009, 21500367, 20021008, 19680020, 22115005]
- US National Institutes of Health [GM53395, NS69720]
- Mitsubishi Foundation
- Human Frontier Science Program
- Grants-in-Aid for Scientific Research [21500367, 24116003, 20021008, 21000009, 22115005, 19680020, 23300148, 24116001] Funding Source: KAKEN
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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. GABA(ergic) inhibition suppressed bulk increases in cytosolic Ca2+ concentrations, whereas it preserved the Ca2+ nanodomains generated by NMDA-type receptors, both of which were necessary for spine shrinkage. Unlike spine enlargement, spine shrinkage spread to neighboring spines (< 15 mu m) and competed with their enlargement, and this process involved the actin-depolymerizing factor ADF/cofilin. Thus, GABA(ergic) inhibition directly suppresses local dendritic Ca2+ transients and strongly promotes the competitive selection of dendritic spines.
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