Cell Reports
Volume 26, Issue 12, 19 March 2019, Pages 3284-3297.e3
Journal home page for Cell Reports

Article
Nanoscale Subsynaptic Domains Underlie the Organization of the Inhibitory Synapse

https://doi.org/10.1016/j.celrep.2019.02.070Get rights and content
Under a Creative Commons license
open access

Highlights

  • Inhibitory synapses are composed of nanoscale subsynaptic domains (SSDs)

  • Gephyrin and GABAAR SSDs closely associate and are dependent on each other

  • GABAAR SSDs are closely associated with presynaptic active-zone SSDs

  • Inhibitory synapses recruit additional SSDs during activity-dependent growth

Summary

Inhibitory synapses mediate the majority of synaptic inhibition in the brain, thereby controlling neuronal excitability, firing, and plasticity. Although essential for neuronal function, the central question of how these synapses are organized at the subsynaptic level remains unanswered. Here, we use three-dimensional (3D) super-resolution microscopy to image key components of the inhibitory postsynaptic domain and presynaptic terminal, revealing that inhibitory synapses are organized into nanoscale subsynaptic domains (SSDs) of the gephyrin scaffold, GABAARs and the active-zone protein Rab3-interacting molecule (RIM). Gephyrin SSDs cluster GABAAR SSDs, demonstrating nanoscale architectural interdependence between scaffold and receptor. GABAAR SSDs strongly associate with active-zone RIM SSDs, indicating an important role for GABAAR nanoscale organization near sites of GABA release. Finally, we find that in response to elevated activity, synapse growth is mediated by an increase in the number of postsynaptic SSDs, suggesting a modular mechanism for increasing inhibitory synaptic strength.

Keywords

GABAA receptor
gephyrin
RIM
VGAT
super-resolution nanoscopy
inhibitory synapse
homeostatic plasticity
structured illumination microscopy

Cited by (0)

2

Lead Contact