Spine Ca2+Signaling in Spike-Timing-Dependent Plasticity
Open accessAbstract
Calcium is a second messenger, which can trigger the modification of synaptic efficacy. We investigated the question of whether a differential rise in postsynaptic Ca 2+([Ca 2+]i) alone is sufficient to account for the induction of long-term potentiation (LTP) and long-term depression (LTD) of EPSPs in the basal dendrites of layer 2/3 pyramidal neurons of the somatosensory cortex. Volume-averaged [Ca 2+]i transients were measured in spines of the basal dendritic arbor for spike-timing-dependent plasticity induction protocols. The rise in [Ca 2+]i was uncorrelated to the direction of the change in synaptic efficacy, because several pairing protocols evoked similar spine [Ca 2+]i transients but resulted in either LTP or LTD. The sequence dependence of near-coincident presynaptic and postsynaptic activity on the direction of changes in synaptic strength suggested that LTP and LTD were induced by two processes, which were controlled separately by postsynaptic [Ca 2+]i levels. Activation of voltage-dependent Ca 2+channels before metabotropic glutamate receptors (mGluRs) resulted in the phospholipase C-dependent (PLC-dependent) synthesis of endocannabinoids, which acted as a retrograde messenger to induce LTD. LTP required a large [Ca 2+]i transient evoked by NMDA receptor activation. Blocking mGluRs abolished the induction of LTD and uncovered the Ca 2+-dependent induction of LTP. We conclude that the volume-averaged peak elevation of [Ca 2+]i in spines of layer 2/3 pyramids determines the magnitude of long-term changes in synaptic efficacy. The direction of the change is controlled, however, via a mGluR-coupled signaling cascade. mGluRs act in conjunction with PLC as sequence-sensitive coincidence detectors when postsynaptic precede presynaptic action potentials to induce LTD. Thus presumably two different Ca 2+sensors in spines control the induction of spike-timing-dependent synaptic plasticity.
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Such synchronous events result in only a short-lasting influx of Ca2+ through NMDA receptors during each spike (<2 μM).
“Given that such synchronous events result in only a short-lasting influx of Ca2+ through NMDA receptors during each spike (<2 μM) (24, 25), postsynaptic spikes must play the key role in the exocytosis of BDNF; for example, involving [Ca2+]i increases in the dendritic shaft via voltage-gated Ca2+ channels.”
From Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines (2008) · cites this paper as [25]
The section on NMDARs and VDCCs reports calcium transients during EPSP–action-potential pairing and shows that blocking NMDARs substantially reduces them. The calcium-imaging section describes relative fluorescence measurements, not an absolute influx below 2 μM during each spike; the paper therefore supports the NMDAR contribution but not the stated magnitude or per-spike characterization. No page numbers are available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPostsynaptic spikes must play the key role in the exocytosis of BDNF.
“Given that such synchronous events result in only a short-lasting influx of Ca2+ through NMDA receptors during each spike (<2 μM) (24, 25), postsynaptic spikes must play the key role in the exocytosis of BDNF; for example, involving [Ca2+]i increases in the dendritic shaft via voltage-gated Ca2+ channels.”
From Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines (2008) · cites this paper as [25]
The citation appears after the sentence’s statement about NMDA-receptor calcium influx; the BDNF-exocytosis conclusion follows as the citing authors’ inference. The source’s sections on calcium influx and postsynaptic calcium transients discuss spike-related calcium signaling and synaptic plasticity, but do not address BDNF exocytosis (searched: BDNF, secretion, exocytosis). (LLM, conf=0.76)
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- Authors
- Nevian, T., & Sakmann, B.
- Affiliations
- Max Planck Society (DE)
- University of Bern (CH)
- ORCID
- Nevian, Thomas
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-10-25
- Volume
- 26
- Issue
- 43
- Pages
- 11001-11013
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674669
- OpenAlex
- W1990501032
- Cited by
- 458
- References
- 4
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 23 · 2023: 16 · 2022: 19 · 2021: 17 · 2020: 24 · 2019: 20 · 2018: 23 · 2017: 17 · 2016: 27 · 2015: 20 · 2014: 24 · 2013: 24 · 2012: 28
- FWCI
- 12.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- spike-timing-dependent plasticity, long-term potentiation, long-term depression, metabotropic glutamate receptors, phospholipase C, endocannabinoids, NMDA receptor, voltage-gated calcium channels, coincidence detection, synaptic plasticity, retrograde signaling
- MeSH terms
- Action Potentials, Animals, Calcium, Neuronal Plasticity, Time Factors, Signal Transduction, Rats, Wistar, Long-Term Potentiation, Pyramidal Cells, Excitatory Postsynaptic Potentials, Calcium Signaling, Calcium Channels, L-Type, Dendritic Spines, Rats
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