Optogenetic Control of Synaptic Composition and Function
Open accessAbstract
The molecular composition of the postsynaptic membrane is sculpted by synaptic activity. During synaptic plasticity at excitatory synapses, numerous structural, signaling, and receptor molecules concentrate at the postsynaptic density (PSD) to regulate synaptic strength. We developed an approach that uses light to tune the abundance of specific molecules in the PSD. We used this approach to investigate the relationship between the number of AMPA-type glutamate receptors in the PSD and synaptic strength. Surprisingly, adding more AMPA receptors to excitatory contacts had little effect on synaptic strength. Instead, we observed increased excitatory input through the apparent addition of new functional sites. Our data support a model where adding AMPA receptors is sufficient to activate synapses that had few receptors to begin with, but that additional remodeling events are required to strengthen established synapses. More broadly, this approach introduces the precise spatiotemporal control of optogenetics to the molecular control of synaptic function.
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Activity-dependent synaptic recruitment of AMPARs may involve two steps: delivery to the PSD, then addition to AMPAR clusters in the nanocolumn.
“It is suggested that activity-dependent synaptic recruitment of AMPARs may involve two steps (259, 261). First, AMPARs are delivered to the PSD, but this is not enough to increase synaptic strength. Second, the newly recruited AMPARs are added to AMPAR clusters in the nanocolumn.”
From Synaptic memory and CaMKII (2023) · cites this paper as [261]
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Cites
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“Indeed, recent studies have demonstrated that the PSD is a heterogeneous structure, with different postsynaptic scaffold complexes organizing neurotransmitter receptors into distinct nanodomains within the PSD (MacGillavry et al., 2013; Nair et al., 2013; Tang et al., 2016).”
InfluentialStructural and Molecular Remodeling of Dendritic Spine Substructures during Long-Term Potentiation
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Franks, K. M., Stevens, C. F., & Sejnowski, T. J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03186.2003 · Cited by 224 · cited 1× · see citing works
“Given the low affinity of AMPA receptors for glutamate, models of quantal synaptic transmission restrict postsynaptic AMPA receptor activation to subsynaptic hotspots, 250 nm in diameter, apposed to presynaptic vesicle release sites (Franks et al., 2003; Raghavachari and Lisman, 2004).”
Properties of Quantal Transmission at CA1 Synapses
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“In another example, synaptic transmission in mice harboring engineered AKAP79/150 with impaired calcineurin binding is primarily mediated by high-conductance, GluA2lacking AMPA receptors, yet quantal amplitude is not altered (Sanderson et al., 2012).”
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Cited by
Sorted by citations
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Self-citationNicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“It is suggested that activity-dependent synaptic recruitment of AMPARs may involve two steps (259, 261).”
Background
- Authors
- Sinnen, B. L., Bowen, A. B., Forte, J. S., Hiester, B. G., Crosby, K. C., Gibson, E. S., Dell’Acqua, M. L., & Kennedy, M. J.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Kennedy, Matthew J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 93
- Issue
- 3
- Pages
- 646-660.e5
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5300939
- OpenAlex
- W2582950460
- Cited by
- 124
- References
- 10
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 14 · 2022: 9 · 2021: 16 · 2020: 16 · 2019: 13 · 2018: 26 · 2017: 11
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- The McKnight Foundation (T32AA007464)
- The Pew Charitable Trusts (T32HD041697)
- The Brain Research Foundation (NS040701, T32GM007635)
- The Brain and Behavior Research Foundation (NS092421)
- The Boettcher Foundation (NS082271)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- optogenetics, postsynaptic density, AMPA receptors, synaptic plasticity, synaptic efficacy, excitatory synapses, synaptic remodeling
- MeSH terms
- Animals, Hippocampus, Neuronal Plasticity, Neurons, Synapses, Synaptic Membranes, Rats, Sprague-Dawley, Long-Term Potentiation, Receptors, AMPA, Patch-Clamp Techniques, Arabidopsis Proteins, Rats, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cryptochromes, Post-Synaptic Density, Optogenetics
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