Proline-rich protein 7/transmembrane adapter protein 3 (Prr7) is down-regulated in dendrites of rat hippocampal neurons, and this is necessary for homeostatic synaptic depression (HSD) induced by a chronic increase in network activity resulting from a blockade of inhibitory synaptic transmission by picrotoxin (PTX) (Inouye et al. 2022). Two activity-regulated miRNAs, miR-329-3p and miR-495-3p, inhibit Prr7 mRNA translation and are required for HSD. Prr7 knockdown reduces expression of the synaptic scaffolding protein SPAR, which is rescued by pharmacological inhibition of CDK5, indicating a role of the Prr7 protein in the maintenance of excitatory synapses via protection of SPAR from degradation. Thus, an HSD mechanism is established in which chronic activity leads to miR-329- and miR-495-mediated Prr7 reduction upstream of the CDK5-SPAR pathway (Hrdinka et al. 2011).