Structure and function of axo-axonic inhibition

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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.
Funding Information
  • Intelligence Advanced Research Projects Activity (D16PC00003)
  • Intelligence Advanced Research Projects Activity (D16PC00004)
  • Intelligence Advanced Research Projects Activity (D16PC0005)
  • National Institute of Neurological Disorders and Stroke (U19 NS104648)
  • Army Research Office (W911NF-12-1-0594)
  • National Eye Institute (R01 EY027036)
  • National Institute of Mental Health (U01 MH114824)
  • National Institute of Neurological Disorders and Strokescience (R01 NS104926)
  • National Institute of Mental Health (RF1MH117815)
  • Mathers Foundation

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