Binary and analog variation of synapses between cortical pyramidal neurons
- Princeton University, United States
- Allen Institute for Brain Science, United States
- Baylor College of Medicine, United States
Abstract
Learning from experience depends at least in part on changes in neuronal connections. We present the largest map of connectivity to date between cortical neurons of a defined type (L2/3 pyramidal cells in mouse primary visual cortex), which was enabled by automated analysis of serial section electron microscopy images with improved handling of image defects (250×140×90 μm3 volume). We used the map to identify constraints on the learning algorithms employed by the cortex. Previous cortical studies modeled a continuum of synapse sizes by a log-normal distribution. A continuum is consistent with most neural network models of learning, in which synaptic strength is a continuously graded analog variable. Here we show that synapse size, when restricted to synapses between L2/3 pyramidal cells, is well-modeled by the sum of a binary variable and an analog variable drawn from a log-normal distribution. Two synapses sharing the same presynaptic and postsynaptic cells are known to be correlated in size . We show that the binary variables of the two synapses are highly correlated, while the analog variables are not. Binary variation could be the outcome of a Hebbian or other synaptic plasticity rule depending on activity signals that are relatively uniform across neuronal arbors, while analog variation may be dominated by other influences such as spontaneous dynamical fluctuations. We discuss the implications for the longstanding hypothesis that activity-dependent plasticity switches synapses between bistable states.
Data availability
All data acquired and produced for this project are available on https://www.microns-explorer.org/phase1
Article and author information
Author details
Emmanouil Froudarakis
Casey M Schneider-Mizell
Nuno Macarico da Costa
Funding
Intelligence Advanced Research Projects Activity (D16PC00003)
- Sven Dorkenwald
- Nicholas L Turner
- Thomas Macrina
- Kisuk Lee
- Ran Lu
- Jingpeng Wu
- Agnes L Bodor
- Adam A Bleckert
- Derrick Brittain
- Nico Kemnitz
- William M Silversmith
- Dodam Ih
- Jonathan Zung
- Aleksandar Zlateski
- Ignacio Tartavull
- Szi-Chieh Yu
- Sergiy Popovych
- William Wong
- Manuel Castro
- Chris S Jordan
- Alyssa M Wilson
- Emmanouil Froudarakis
- JoAnn Buchanan
- Marc M Takeno
- Russel Torres
- Gayathri Mahalingam
- Forrest Collman
- Casey M Schneider-Mizell
- Daniel J Bumbarger
- Yang Li
- Lynne Becker
- Shelby Suckow
- Jacob Reimer
- Andreas Savas Tolias
- Nuno Macarico da Costa
- R Clay Reid
- H Sebastian Seung
G. Harold and Leila Y. Mathers Foundation
- H Sebastian Seung
Intelligence Advanced Research Projects Activity (D16PC00004)
- Sven Dorkenwald
- Nicholas L Turner
- Thomas Macrina
- Kisuk Lee
- Ran Lu
- Jingpeng Wu
- Agnes L Bodor
- Adam A Bleckert
- Derrick Brittain
- Nico Kemnitz
- William M Silversmith
- Dodam Ih
- Jonathan Zung
- Aleksandar Zlateski
- Ignacio Tartavull
- Szi-Chieh Yu
- Sergiy Popovych
- William Wong
- Manuel Castro
- Chris S Jordan
- Alyssa M Wilson
- Emmanouil Froudarakis
- JoAnn Buchanan
- Marc M Takeno
- Russel Torres
- Gayathri Mahalingam
- Forrest Collman
- Casey M Schneider-Mizell
- Daniel J Bumbarger
- Yang Li
- Lynne Becker
- Shelby Suckow
- Jacob Reimer
- Andreas Savas Tolias
- Nuno Macarico da Costa
- R Clay Reid
- H Sebastian Seung
Intelligence Advanced Research Projects Activity (D16PC00005)
- Sven Dorkenwald
- Nicholas L Turner
- Thomas Macrina
- Kisuk Lee
- Ran Lu
- Jingpeng Wu
- Agnes L Bodor
- Adam A Bleckert
- Derrick Brittain
- Nico Kemnitz
- William M Silversmith
- Dodam Ih
- Jonathan Zung
- Aleksandar Zlateski
- Ignacio Tartavull
- Szi-Chieh Yu
- Sergiy Popovych
- William Wong
- Manuel Castro
- Chris S Jordan
- Alyssa M Wilson
- Emmanouil Froudarakis
- JoAnn Buchanan
- Marc M Takeno
- Russel Torres
- Gayathri Mahalingam
- Forrest Collman
- Casey M Schneider-Mizell
- Daniel J Bumbarger
- Yang Li
- Lynne Becker
- Shelby Suckow
- Jacob Reimer
- Andreas Savas Tolias
- Nuno Macarico da Costa
- R Clay Reid
- H Sebastian Seung
National Institute of Neurological Disorders and Stroke (U19 NS104648)
- H Sebastian Seung
Army Research Office (W911NF-12-1-0594)
- H Sebastian Seung
National Eye Institute (R01 EY027036)
- H Sebastian Seung
National Institute of Mental Health (U01 MH114824)
- H Sebastian Seung
National Institute of Neurological Disorders and Stroke (R01 NS104926)
- H Sebastian Seung
National Institute of Mental Health (RF1MH117815)
- H Sebastian Seung
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal procedures were approved by the Institutional Animal Care and Use Committee at the Allen Institute for Brain Science (1503 and 1804) or Baylor College of Medicine (AN-4703).
Reviewing Editor
- Timothy O'Leary, University of Cambridge, United Kingdom
Version history
- Preprint posted: December 31, 2019 (view preprint)
- Received: December 13, 2021
- Accepted: November 15, 2022
- Accepted Manuscript published: November 16, 2022 (version 1)
- Version of Record published: November 28, 2022 (version 2)
Copyright
© 2022, Dorkenwald et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Binary and analog variation of synapses between cortical pyramidal neurons
eLife 11:e76120.
https://doi.org/10.7554/eLife.76120
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