Details

Autor(en) / Beteiligte

• Yang, Xiaojuan
• Le Corronc, Hervé
• Legendre, Pascal
• Triller, Antoine
• Specht, Christian G

Titel

Differential regulation of glycinergic and GABAergic nanocolumns at mixed inhibitory synapses

Ist Teil von

• EMBO reports, 2021-07, Vol.22 (7), p.e52154-n/a

Ort / Verlag

Heidelberg: Blackwell Publishing Ltd

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Super‐resolution imaging has revealed that key synaptic proteins are dynamically organized within sub‐synaptic domains (SSDs). To examine how different inhibitory receptors are regulated, we carried out dual‐color direct stochastic optical reconstruction microscopy (dSTORM) of GlyRs and GABAARs at mixed inhibitory synapses in spinal cord neurons. We show that endogenous GlyRs and GABAARs as well as their common scaffold protein gephyrin form SSDs that align with pre‐synaptic RIM1/2, thus creating trans‐synaptic nanocolumns. Strikingly, GlyRs and GABAARs occupy different sub‐synaptic spaces, exhibiting only a partial overlap at mixed inhibitory synapses. When network activity is increased by 4‐aminopyridine treatment, the GABAAR copy numbers and the number of GABAAR SSDs are reduced, while GlyRs remain largely unchanged. This differential regulation is likely the result of changes in gephyrin phosphorylation that preferentially occurs outside of SSDs. The activity‐dependent regulation of GABAARs versus GlyRs suggests that different signaling pathways control the receptors' sub‐synaptic clustering. Taken together, our data reinforce the notion that the precise sub‐synaptic organization of GlyRs, GABAARs, and gephyrin has functional consequences for the plasticity of mixed inhibitory synapses. SYNOPSIS This study analyzes the internal organization of mixed inhibitory spinal cord synapses using dSTORM and reveals the existence of trans‐synaptic nanocolumns containing GlyRs and GABAARs that are differentially regulated in response to altered network activity. Sub‐synaptic domains (SSDs) are aligned in trans‐synaptic nanocolumns at inhibitory synapses. SSDs formed by GlyRs and GABAARs are differentially spatially organized at mixed inhibitory synapses. GABAARs but not GlyRs show activity‐dependent regulation at mixed inhibitory synapses. Gephyrin phosphorylation is compartmentalized in SSDs within the synaptic scaffold. This study analyzes the internal organization of mixed inhibitory spinal cord synapses using dSTORM and reveals the existence of trans‐synaptic nanocolumns containing GlyRs and GABAARs that are differentially regulated in response to altered network activity.