Structure and function of axo-axonic inhibition
- Allen Institute for Brain Science, United States
- Princeton University, United States
- Baylor College of Medicine, United States
Abstract
Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.
Data availability
Volume electron microscopy and segmentation data is available at https://www.microns-explorer.org/phase1. AIS synapse and PyC structural data are included in Supplemental Data. All other meshes and data tables are on Zenodo (DOI:10.5281/zenodo.5579388). All ChC calcium traces are also on Zenodo (DOI: 10.5281/zenodo.5725826). Analysis code and NEURON models are available at http://github.com/AllenInstitute/ChandelierL23.
Article and author information
Author details
Casey M Schneider-Mizell
Emmanouil Froudarakis
Funding
Intelligence Advanced Research Projects Agency (D16PC00003,D16PC00004,D16PC0005)
- Casey M Schneider-Mizell
- Agnes L Bodor
- Forrest Collman
- Derrick Brittain
- Adam Bleckert
- Sven Dorkenwald
- Nicholas L Turner
- Thomas Macrina
- Kisuk Lee
- Ran Lu
- Jingpeng Wu
- Jun Zhuang
- Anirban Nandi
- Brian Hu
- JoAnn Buchanan
- Marc M Takeno
- Russel Torres
- Gayathri Mahalingam
- Daniel J Bumbarger
- Yang Li
- Thomas Chartrand
- Nico Kemnitz
- William M Silversmith
- Dodam Ih
- Jonathan Zung
- Aleksandar Zlateski
- Ignacio Tartavull
- Sergiy Popovych
- William Wong
- Manuel Castro
- Chris S Jordan
- Emmanouil Froudarakis
- Lynne Becker
- Shelby Suckow
- Jacob Reimer
- Andreas S Tolias
- Costas A Anastassiou
- H Sebastian Seung
- R Clay Reid
- Nuno Maçarico da Costa
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 Strokescience (R01 NS104926)
- H Sebastian Seung
National Institute of Mental Health (RF1MH117815)
- H Sebastian Seung
Mathers Foundation
- H Sebastian Seung
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.Disclaimer: The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of IARPA, DoI/IBC, or the U.S. Government.
Reviewing Editor
- Ronald L Calabrese, Emory University, United States
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).
Version history
- Received: September 9, 2021
- Accepted: November 30, 2021
- Accepted Manuscript published: December 1, 2021 (version 1)
- Version of Record published: January 13, 2022 (version 2)
Copyright
© 2021, Schneider-Mizell 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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Structure and function of axo-axonic inhibition
eLife 10:e73783.
https://doi.org/10.7554/eLife.73783
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