Structure and function of axo-axonic inhibition
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 01, 2021
- Source ID
- 10.7554/elife.73783
Entities
People
- Adam Bleckert
- Agnes L. Bodor
- Aleksandar Zlateski
- Andreas S Tolias
- Anirban Nandi
- Brian Hu
- Casey M Schneider-Mizell
- Chris S. Jordan
- Costas A Anastassiou
- Daniel J. Bumbarger
- Derrick Brittain
- Dodam Ih
- Emmanouil Froudarakis
- Forrest Collman
- Gayathri Mahalingam
- H. Sebastian Seung
- Ignacio Tartavull
- Jacob Reimer
- Jingpeng Wu
- JoAnn Buchanan
- Jonathan Zung
- Jun Zhuang
- Kisuk Lee
- Lynne Becker
- Manuel Castro
- Marc Takeno
- Nicholas L. Turner
- Nico Kemnitz
- Nuno Macarico da Costa
- R Clay Reid
- Ran Lu
- Russel M Torres
- Sergiy Popovych
- Shelby Suckow
- Sven Dorkenwald
- Thomas Chartrand
- Thomas Macrina
- William Silversmith
- William Wong
- Yang Li
Organizations
- Army Research Office
- Baylor College of Medicine
- G. Harold & Leila Y. Mathers Foundation
- Intelligence Advanced Research Projects Activity
- Massachusetts Institute of Technology
- National Eye Institute
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- Princeton University
- Rice University
- University of British Columbia