Activity-dependent movements of postsynaptic scaffolds at inhibitory synapses

Dendritic spines show an activity-dependent cytoskeleton-based remodeling coupled with variations in receptor number and the functional properties of excitatory synapses. In this study, we analyzed the dynamics of gephyrin containing inhibitory postsynaptic scaffolds imaging a Venus::gephyrin (VeGe) chimera in dissociated spinal cord neurons. We provide evidence that the postsynaptic scaffolds at mature synapses display a submicrometric rapid lateral motion and are continuously moving on the dendritic shaft. This dynamic behavior is calcium dependent and is controlled by the cytoskeleton. Minute rearrangement within the gephyrin scaffold as well as the scaffold lateral displacements are F-actin dependent. The lateral movements are counteracted by microtubules. Moreover, the action of the potassium channel blocker 4-aminopyridine and receptor antagonists indicate that the dynamics of postsynaptic gephyrin scaffolds are controlled by synaptic activity.