MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons

Significance Homeostatic mechanisms maintain stable neuronal and circuit function in the brain, in particular during development and learning, when synapses undergo constant changes. Synaptic scaling is a form of homeostatic synaptic plasticity responsible for maintaining neuronal network activity within a physiological range, mainly through the regulation of AMPA receptors at synaptic sites. However, the intrinsic mechanisms promoting synaptic scaling are still largely unknown. Here, we have uncovered miR-186-5p as an activity-regulated miRNA, which targets the GluA2 AMPA receptor subunit and mediates synaptic scaling triggered by prolonged blockade of synaptic activity.