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Cited by 244Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

Single-Cell Optogenetic Excitation Drives Homeostatic Synaptic Depression

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Goold, Carleton P., Nicoll, Roger A.·2010·Neuron
DOI 10.1016/j.neuron.2010.09.020PMC PMC3111089
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Abstract

Homeostatic processes have been proposed to explain the discrepancy between the dynamics of synaptic plasticity and the stability of brain function. Forms of synaptic plasticity such as long-term potentiation alter synaptic activity in a synapse- and cell-specific fashion. Although network-wide excitation triggers compensatory homeostatic changes, it is unknown whether neurons initiate homeostatic synaptic changes in response to cell-autonomous increases in excitation. Here we employ optogenetic tools to cell-autonomously excite CA1 pyramidal neurons and find that a compensatory postsynaptic depression of both AMPAR and NMDAR function results. Elevated calcium influx through L-type calcium channels leads to activation of a pathway involving CaM kinase kinase and CaM kinase 4 that induces synaptic depression of AMPAR and NMDAR responses. The synaptic depression of AMPARs but not of NMDARs requires protein synthesis and the GluA2 AMPAR subunit, indicating that downstream of CaM kinase activation divergent pathways regulate homeostatic AMPAR and NMDAR depression.

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  • Scaling down in response to elevated network activity is a cell-autonomous function of postsynaptic firing, and involves enhanced calcium influx, gene transcription, the CaMKK/CaMKIV signaling pathway, and targets the GluA2 subunit.

    “Like scaling up, scaling down in response to elevated network activity is a cell-autonomous function of postsynaptic firing, and involves enhanced calcium influx (Fig. 2), gene transcription, the CaMKK/CaMKIV signaling pathway, and targets the GluA2 subunit (Goold and Nicoll 2010).”

    From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Goold and Nicoll 2010

    The Discussion reports that cell-autonomous excitation drives calcium-dependent synaptic depression through CaMKK/CaMK4. It also limits the transcription and GluA2 requirements to AMPAR depression: NMDAR depression does not require them. The citing sentence omits that distinction when describing scaling down generally. (LLM, conf=0.85)

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  • CaMKII contributes to baseline synaptic transmission, as shown by peptide inhibitors, RNAi, and CRISPR.

    “The first evidence that CaMKII contributes to synaptic transmission came from expression of peptide inhibitors (150, 154).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [150]

    The Results section reports that expression of the CaMKII peptide inhibitors CaMKIIN or AIP reduced synaptic AMPAR responses, supporting a contribution to baseline synaptic transmission. The copy does not establish that this was the first evidence, and its reported shRNA experiment targets CaMK4, not CaMKII; it provides no CRISPR evidence for CaMKII. (LLM, conf=0.86)

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Authors
Goold, C. P., & Nicoll, R. A.
Affiliations
University of California, San Francisco (US)
Corresponding author
Nicoll, Roger A.
ORCID
Nicoll, Roger A.
Venue
Neuron
Publisher
Elsevier BV
Published
2010-11
Volume
68
Issue
3
Pages
512-528
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2010.09.020
PMC
PMC3111089
OpenAlex
W1986627859
Cited by
244
References
5
Citations by year
2026: 3 · 2025: 11 · 2024: 13 · 2023: 10 · 2022: 7 · 2021: 22 · 2020: 16 · 2019: 13 · 2018: 15 · 2017: 13 · 2016: 17 · 2015: 16 · 2014: 13 · 2013: 30 · 2012: 23
FWCI
9.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation
  • National Institute of Mental Health
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
synaptic plasticity, CA1 pyramidal neurons, L-type calcium channels, GluR2 subunit, protein synthesis, hippocampus, long-term potentiation
MeSH terms
Channelrhodopsins, Animals, Brain, Electrophysiology, Enzyme Inhibitors, Homeostasis, Neuronal Plasticity, Photic Stimulation, Synapses, Protein Biosynthesis, Receptors, N-Methyl-D-Aspartate, Pyramidal Cells, Receptors, AMPA, Patch-Clamp Techniques, Calcium Signaling, Calcium Channels, L-Type, Mice, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 4, Calcium-Calmodulin-Dependent Protein Kinase Kinase, CA1 Region, Hippocampal, In Vitro Techniques

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