GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling
Open accessAbstract
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 GABAA receptors shortly before action potentials. GABAergic 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 μm) and competed with their enlargement, and this process involved the actin-depolymerizing factor ADF/cofilin. Thus, GABAergic inhibition directly suppresses local dendritic Ca2+ transients and strongly promotes the competitive selection of dendritic spines.
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The primary effect of sleep might be to reduce overall network activity and connectivity at excitatory synapses by increasing inhibition, pushing cortical E-I balance toward increased synaptic inhibition.
“The primary effect of sleep might well be to reduce overall network activity, and connectivity at excitatory synapses 233 by increasing inhibition, i.e., by pushing the cortical E-I balance toward increased synaptic inhibition.”
From Sleep—A brain-state serving systems memory consolidation (2023) · cites this paper as [233]
The Results (Spine shrinkage by two-color glutamate and GABA uncaging; page unavailable) report GABA-associated spine shrinkage, elimination, and reduced glutamate sensitivity, supporting a local mechanism for weakening excitatory connections. The paper does not examine sleep or establish that sleep reduces overall network activity or shifts cortical excitation–inhibition balance toward inhibition. (LLM, conf=0.87)
Experimental — accuracy not yet measuredExogenous cofilins diffused along a dendrite and induced the spreading of spine shrinkage, similar to that induced by LFS or spike-timing dependent induction.
“These experiments indicate that exogenous cofilins diffused along a dendrite and induced the spreading of spine shrinkage, similar to that induced by LFS (Supplementary Fig. S1) or spike-timing dependent induction9.”
From State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines (2016) · cites this paper as [9]
Spine shrinkage tends to spread, as in LTD.
“It has been reported that spine shrinkage tends to spread919 as in the case with LTD202122.”
From State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines (2016) · cites this paper as [9]
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Self-citation
- Authors
- Hayama, T., Noguchi, J., Watanabe, S., Takahashi, N., Hayashi-Takagi, A., Ellis-Davies, G. C. R., Matsuzaki, M., & Kasai, H.
- Affiliations
- Japan Science and Technology Agency (JP)
- National Institute for Basic Biology (JP)
- Corresponding author
- Kasai, Haruo
- Venue
- Nature Neuroscience
- Published
- 2013-08-25
- Volume
- 16
- Issue
- 10
- Pages
- 1409-1416
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4135703
- OpenAlex
- W2063856415
- Semantic Scholar
- 701c709cd74e18e7a3f960e45b518eb1729c2738
- Cited by
- 193
- References
- 55
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 15 · 2023: 12 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 15 · 2018: 15 · 2017: 16 · 2016: 23 · 2015: 16 · 2014: 16 · 2013: 1
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (23300148, 24116001, 24116003, 21000009)
- National Institute of General Medical Sciences (GM 53395, R01GM053395)
- National Institute of Neurological Disorders and Stroke (R01NS069720, NS69720)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- GABA, dendritic spines, synaptic competition, GABAA receptor, NMDA receptor, calcium nanodomains, calcium signaling, ADF/cofilin, actin cytoskeleton, glutamate uncaging, CA1 pyramidal neurons, synaptic plasticity, dendritic calcium transients
- MeSH terms
- Animals, Female, gamma-Aminobutyric Acid, Hippocampus, Male, Organ Culture Techniques, Rats, Sprague-Dawley, Calcium Signaling, Dendritic Spines, Rats
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