Activity-Dependent Plasticity of Axo-axonic Synapses at the Axon Initial Segment

Neuron. 2020 Apr 22;106(2):265-276.e6. doi: 10.1016/j.neuron.2020.01.037. Epub 2020 Feb 27.


The activity-dependent rules that govern the wiring of GABAergic interneurons are not well understood. Chandelier cells (ChCs) are a type of GABAergic interneuron that control pyramidal cell output through axo-axonic synapses that target the axon initial segment. In vivo imaging of ChCs during development uncovered a narrow window (P12-P18) over which axons arborized and formed connections. We found that increases in the activity of either pyramidal cells or individual ChCs during this temporal window result in a reversible decrease in axo-axonic connections. Voltage imaging of GABAergic transmission at the axon initial segment (AIS) showed that axo-axonic synapses were depolarizing during this period. Identical manipulations of network activity in older mice (P40-P46), when ChC synapses are inhibitory, resulted instead in an increase in axo-axonic synapses. We propose that the direction of ChC synaptic plasticity follows homeostatic rules that depend on the polarity of axo-axonic synapses.

Keywords: Chandelier; GABA; activity-dependent; axo-axonic; axon initial segment; development; homeostatic; interneuron; plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Axon Initial Segment / physiology*
  • Axons / physiology*
  • Interneurons / physiology
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity / physiology*
  • Presynaptic Terminals / physiology
  • Pyramidal Cells / physiology
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / growth & development
  • Somatosensory Cortex / physiology
  • Synapses / physiology*
  • Thyroid Nuclear Factor 1 / genetics
  • gamma-Aminobutyric Acid / physiology


  • Nkx2-1 protein, mouse
  • Thyroid Nuclear Factor 1
  • gamma-Aminobutyric Acid