Significance More than 95% of excitatory synaptic contacts form on spines, highly motile dendritic protrusions that emerge, grow, or disappear in response to specific patterns of synaptic activity. This physical rearrangement is most prominent during critical periods of early postnatal life, when young brains are reshaped by experience to encode certain kinds of information. We reveal a mechanism whereby juvenile NMDA-type glutamate receptors containing GluN3A subunits regulate spine rearrangements by controlling the function of G protein-coupled receptor kinase-interacting protein (GIT1). GIT1 is a postsynaptic scaffold that couples stimuli promoting spine maturation to sustained cytoskeletal rearrangements. Binding to GluN3A limits the synaptic targeting of GIT1 and its ability to recruit actin regulators in an activity-dependent manner, providing a mechanism to limit the maturation of nonused synapses.

Background: Heterodimerization of GABAB1 and GABAB2 subunits is required for functional GABABRs.Results: GABABR subunits are differentially regulated by activation of synaptic or extrasynaptic NMDARs.Conclusion: GABABR trafficking and function is regulated by NMDARs.Significance: GABABRs are potential targets for treating diseases such as stroke and cerebral ischemia.