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Cited by 119Neuroscience and Neuropharmacology ResearchIon channel regulation and functionNeural dynamics and brain function

Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines

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Bloodgood, Brenda L., Giessel, Andrew J., Sabatini, Bernardo L.·2009·PLoS Biology
DOI 10.1371/journal.pbio.1000190PMC PMC2734993
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Abstract

Excitatory synapses on mammalian principal neurons are typically formed onto dendritic spines, which consist of a bulbous head separated from the parent dendrite by a thin neck. Although activation of voltage-gated channels in the spine and stimulus-evoked constriction of the spine neck can influence synaptic signals, the contribution of electrical filtering by the spine neck to basal synaptic transmission is largely unknown. Here we use spine and dendrite calcium (Ca) imaging combined with 2-photon laser photolysis of caged glutamate to assess the impact of electrical filtering imposed by the spine morphology on synaptic Ca transients. We find that in apical spines of CA1 hippocampal neurons, the spine neck creates a barrier to the propagation of current, which causes a voltage drop and results in spatially inhomogeneous activation of voltage-gated Ca channels (VGCCs) on a micron length scale. Furthermore, AMPA and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively) that are colocalized on individual spine heads interact to produce two kinetically and mechanistically distinct phases of synaptically evoked Ca influx. Rapid depolarization of the spine triggers a brief and large Ca current whose amplitude is regulated in a graded manner by the number of open AMPARs and whose duration is terminated by the opening of small conductance Ca-activated potassium (SK) channels. A slower phase of Ca influx is independent of AMPAR opening and is determined by the number of open NMDARs and the post-stimulus potential in the spine. Biphasic synaptic Ca influx only occurs when AMPARs and NMDARs are coactive within an individual spine. These results demonstrate that the morphology of dendritic spines endows associated synapses with specialized modes of signaling and permits the graded and independent control of multiple phases of synaptic Ca influx.

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  • Classes of voltage gated calcium channels exclusively localize to spines but not dendrites and cooperate with other calcium channels to shape local depolarization and synaptic plasticity.

    “Such an effect is strengthened by the existence of classes of voltage gated calcium channels that exclusively localize to spines but not dendrites and cooperate with other calcium channels to shape local depolarization and synaptic plasticity (Bloodgood and Sabatini, 2007b; Bloodgood et al., 2009).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Bloodgood et al., 2009

    The Introduction states that SNX-482-sensitive voltage-gated calcium channels are found in spine heads but not dendritic shafts. The Results and Discussion describe localized calcium influx involving voltage-sensitive sources and NMDARs, but the Discussion presents effects on plasticity-related signaling as a possibility, not a demonstrated outcome. The paper does not establish that these channels cooperate with other calcium channels to shape local depolarization and synaptic plasticity as claimed. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Opening of sodium and calcium channels boosts local depolarization, while opening of potassium channels decreases local input resistance and results in smaller synaptic potentials.

    “Opening of sodium and calcium channels boosts local depolarization (Araya et al., 2007; Bloodgood et al., 2009; Holbro et al., 2010; Carter et al., 2012; Hao and Oertner, 2012), while opening of potassium channels decreases local input resistance and results in smaller synaptic potentials (Ngo-Anh et al., 2005; Giessel and Sabatini, 2010).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Bloodgood et al., 2009

    The Results section (‘Biphasic Synaptic Ca Influx and Graded Control by AMPARs’; page unavailable) says AMPARs modulate the amplitude of the synaptic potential in the spine, supporting a role for channel opening in local depolarization. But the paper describes voltage-gated calcium channels as being activated by synaptic depolarization, and says voltage-gated sodium channels were blocked in its experiments; it does not establish that opening both sodium and calcium channels boosts local depolarization. The potassium-channel clause is attributed to other citations, not this paper. (LLM, conf=0.85)

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Cites

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Authors
Bloodgood, B. L., Giessel, A. J., & Sabatini, B. L.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Sabatini, Bernardo L.
ORCID
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2009-09-15
Volume
7
Issue
9
Pages
e1000190
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.1000190
PMC
PMC2734993
OpenAlex
W2161713570
Cited by
119
References
3
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 8 · 2014: 11 · 2013: 12 · 2012: 10
FWCI
3.60
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of Neurological Disorders and Stroke (R01NS046579, R37NS046579, NS046579)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
dendritic spines, voltage-gated calcium channels, AMPA receptors, NMDA receptor, small conductance calcium-activated potassium channels, CA1 hippocampal neurons, synaptic transmission, calcium imaging
MeSH terms
Animals, Hippocampus, Neural Conduction, Synaptic Transmission, Calcium Channels, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA, Glutamic Acid, Calcium Signaling, Dendritic Spines, Mice, Electrical Synapses, Synaptic Potentials

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