Calcium stores regulate the polarity and input specificity of synaptic modification
Abstract
Activity-induced synaptic modification is essential for the development and plasticity of the nervous system. Repetitive correlated activation of pre- and postsynaptic neurons can induce persistent enhancement or decrement of synaptic efficacy, commonly referred to as long-term potentiation or depression (LTP or LTD). An important unresolved issue is whether and to what extent LTP and LTD are restricted to the activated synapses. Here we show that, in the CA1 region of the hippocampus, reduction of postsynaptic calcium influx by partial blockade of NMDA (N-methyl-D-aspartate) receptors results in a conversion of LTP to LTD and a loss of input specificity normally associated with LTP, with LTD appearing at heterosynaptic inputs. The induction of LTD at homo- and heterosynaptic sites requires functional ryanodine receptors and inositol triphosphate (InsP3) receptors, respectively. Functional blockade or genetic deletion of type 1 InsP3 receptors led to a conversion of LTD to LTP and elimination of heterosynaptic LTD, whereas blocking ryanodine receptors eliminated only homosynaptic LTD. Thus, postsynaptic Ca2+, deriving from Ca2+ influx and differential release of Ca2+ from internal stores through ryanodine and InsP3 receptors, regulates both the polarity and input specificity of activity-induced synaptic modification.
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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 [20]
dp-cofilin efficiently diffused along dendrites, enabling heterosynaptic shrinkage of spines along dendrites.
“Despite its binding to F-actins, we demonstrated that dp-cofilin efficiently diffused along dendrites, enabling heterosynaptic shrinkage of spines along dendrites, which was consistent with the spread of LTD along dendrites202122.”
From State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines (2016) · cites this paper as [20]
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- Authors
- Nishiyama, M., Hong, K., Mikoshiba, K., Poo, M.-M., & Kato, K.
- Affiliations
- University of California San Diego (US)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Poo, Mu-ming
- Venue
- Nature
- Published
- 2000-11
- Volume
- 408
- Issue
- 6812
- Pages
- 584-588
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1589692855
- Cited by
- 635
- References
- 3
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 16 · 2023: 11 · 2022: 14 · 2021: 17 · 2020: 10 · 2019: 14 · 2018: 28 · 2017: 16 · 2016: 20 · 2015: 27 · 2014: 24 · 2013: 26 · 2012: 18
- FWCI
- 10.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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 › Molecular Biology › Ion channel regulation and function
- Keywords
- long-term potentiation, long-term depression, synaptic plasticity, input specificity, heterosynaptic plasticity, ryanodine receptor, IP3 receptor, NMDA receptor blockade, hippocampal CA1, calcium influx
- MeSH terms
- Animals, Calcium, Hippocampus, Male, Models, Neurological, Neurons, Synapses, Calcium Channels, Inositol 1,4,5-Trisphosphate, N-Methylaspartate, Long-Term Potentiation, Receptors, Cytoplasmic and Nuclear, Excitatory Postsynaptic Potentials, Rats, Inositol 1,4,5-Trisphosphate Receptors, In Vitro Techniques
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