RT Journal Article SR Electronic T1 Rapid homeostatic modulation of transsynaptic nanocolumn rings JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.15.448550 DO 10.1101/2021.06.15.448550 A1 Paola Muttathukunnel A1 Patrick Frei A1 Sarah Perry A1 Dion Dickman A1 Martin Müller YR 2021 UL http://biorxiv.org/content/early/2021/06/16/2021.06.15.448550.abstract AB Robust neural information transfer relies on a delicate molecular nano-architecture of chemical synapses. Neurotransmitter release is controlled by a specific arrangement of proteins within presynaptic active zones. How the specific presynaptic molecular architecture relates to postsynaptic organization, and how synaptic nano-architecture is transsynaptically regulated to achieve stable synaptic transmission remains enigmatic. Using time-gated stimulated emission depletion (gSTED) microscopy at the Drosophila neuromuscular junction, we here find that presynaptic nano-rings formed by the active-zone scaffold Bruchpilot (Brp) precisely align with postsynaptic glutamate receptor (GluR) rings. Individual rings harbor ~5 transsynaptically-aligned Brp-GluR ‘nanocolumns’. Intriguingly, acute GluR impairment rapidly triggers the formation of new transsynaptic nanocolumns on the minute time scale during homeostatic plasticity. We reveal distinct phases of structural transsynaptic homeostatic plasticity, with postsynaptic reorganization preceding presynaptic modulation. Finally, the auxiliary GluR subunit Neto-β promotes structural and functional homeostatic plasticity. Thus, transsynaptic nanocolumns arrange in stereotypic rings that are rapidly modulated during homeostatic plasticity to stabilize synaptic efficacy.One Sentence Summary Rapid changes of transsynaptic nanocolumn rings during homeostatic plasticity.Competing Interest StatementThe authors have declared no competing interest.