GluN3A Promotes Dendritic Spine Pruning and Destabilization during Postnatal Development

摘要: Synaptic rearrangements during critical periods of postnatal brain development rely on the correct formation, strengthening, and elimination synapses associated dendritic spines to form functional networks. The balance these processes is thought be regulated by synapse-specific changes in subunit composition NMDA-type glutamate receptors (NMDARs). Among these, nonconventional NMDAR GluN3A has been suggested play a role as molecular brake synaptic maturation. We tested here this hypothesis using confocal time-lapse imaging rat hippocampal organotypic slices assessed GluN3A-containing NMDARs spine dynamics. found that overexpressing reduced density over time, increased elimination, decreased stability. effect overexpression could further enhanced an endocytosis-deficient mutant reproduced silencing adaptor protein PACSIN1, which prevents endocytosis endogenous GluN3A. Conversely, favored Moreover, reexpression more mature tissue reinstated pruning low Mechanistically, stability neurons linked failure plasticity-inducing protocols selectively stabilize was dependent ability bind postsynaptic scaffold GIT1. Together, data provide strong evidence activity-dependent stabilization thereby promoting pruning, suggest expression operates signal for controlling extent timing synapse