Structure and function of axo-axonic inhibition

Casey M. Schneider-Mizell, Agnes L. Bodor, Forrest Collman, Derrick Brittain, Adam A. 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 LiTom 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

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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 axo41 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.

Original languageEnglish (US)
Article numbere73783
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience


  • Cell types
  • Chandelier cell
  • Circuits
  • EM connectomics
  • Mouse visual cortex


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