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Cited by 363Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionMemory and Neural Mechanisms

Local connectivity and synaptic dynamics in mouse and human neocortex

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Campagnola, Luke, Seeman, Stephanie C., Chartrand, Thomas, Kim, Lisa, Hoggarth, Alex, Gamlin, Clare, Ito, Shinya, Trinh, Jessica +81 more·2022·Science
DOI 10.1126/science.abj5861PMC PMC9970277

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Abstract

We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Synaptic properties are heterogeneous in most subclass-to-subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, whereas the strength axis accounts for substantial heterogeneity within the subclass. In the human cortex, excitatory-to-excitatory synaptic dynamics are distinct from those in the mouse cortex and vary with depth across layers 2 and 3.

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  • From a circuit perspective, Sst interneurons are uniquely positioned to exert control over both excitation and inhibition in the cortex as they target excitatory and all other subclasses of inhibitory cortical neurons, but not themselves.

    “From a circuit perspective, Sst interneurons are uniquely positioned to exert control over both excitation and inhibition in the cortex as they target excitatory and all other subclasses of inhibitory cortical neurons, but not themselves91.”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [91]

    The Discussion section on conserved mouse intralaminar circuitry describes Sst cells as broadly inhibiting nearby cells, which supports the claim's broad targeting premise. But the Results section on intralaminar connectivity explicitly reports connections between Sst neurons in every layer and confirms connections between transcriptionally identified Sst cells. Thus, the claim that they do not target themselves is contrary to the paper's findings. (LLM, conf=0.89)

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Authors
Campagnola, L., Seeman, S. C., Chartrand, T., Kim, L., Hoggarth, A., Gamlin, C., Ito, S., Trinh, J., Davoudian, P., Radaelli, C., Kim, M.-H., Hage, T., Braun, T., Alfiler, L., Andrade, J., Bohn, P., Dalley, R., Henry, A., Kebede, S., Mukora, A., Sandman, D., Williams, G., Larsen, R., Teeter, C., Daigle, T. L., Berry, K., Dotson, N., Enstrom, R., Gorham, M., Hupp, M., Dingman Lee, S., Ngo, K., Nicovich, P. R., Potekhina, L., Ransford, S., Gary, A., Goldy, J., McMillen, D., Pham, T., Tieu, M., Siverts, L., Walker, M., Farrell, C., Schroedter, M., Slaughterbeck, C., Cobb, C., Ellenbogen, R., Gwinn, R. P., Keene, C. D., Ko, A. L., Ojemann, J. G., Silbergeld, D. L., Carey, D., Casper, T., Crichton, K., Clark, M., Dee, N., Ellingwood, L., Gloe, J., Kroll, M., Sulc, J., Tung, H., Wadhwani, K., Brouner, K., Egdorf, T., Maxwell, M., McGraw, M., Pom, C. A., Ruiz, A., Bomben, J., Feng, D., Hejazinia, N., Shi, S., Szafer, A., Wakeman, W., Phillips, J., Bernard, A., Esposito, L., D’Orazi, F. D., Sunkin, S., Smith, K., Tasic, B., Arkhipov, A., Sorensen, S., Lein, E., Koch, C., Murphy, G., Zeng, H., & Jarsky, T.
Affiliations
  • Allen Institute for Brain Science (US)
  • Byte Physics, Berlin, Germany.
  • Allen Institute for Brain Science, Seattle, WA, USA.
  • Swedish Medical Center (US)
  • University of Washington (US)
Corresponding author
  • Campagnola, Luke
  • Seeman, Stephanie C.
  • Jarsky, Tim
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-03-11
Volume
375
Issue
6585
Pages
eabj5861-eabj5861
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.abj5861
PMC
PMC9970277
OpenAlex
W4220896689
Cited by
363
References
23
Citations by year
2026: 68 · 2025: 93 · 2024: 99 · 2023: 67 · 2022: 33 · 2021: 1 · 2020: 2
FWCI
32.28
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1rf1mh121274-01, 5u01mh114812-03)
  • National Institute on Aging (P30AG066509)
  • National Institute of Mental Health (RF1 MH121274, U01MH105982, U01MH114812, U19MH114830)
  • National Institute on Drug Abuse (R01DA036909)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
synaptic dynamics, neocortex, local connectivity, excitatory synapses, inhibitory synapses, synaptic heterogeneity, synaptic efficacy, synaptic variability, human cortex, mouse cortex, cortical depth
MeSH terms
Adult, Animals, Female, Humans, Male, Mice, Transgenic, Models, Neurological, Neural Pathways, Synaptic Transmission, Neurons, Synapses, Temporal Lobe, Visual Cortex, Neocortex, Excitatory Postsynaptic Potentials, Mice, Inhibitory Postsynaptic Potentials, Datasets as Topic

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