8.A.202. The Proline-rich Receptor (PrR) Family
The proline-rich protein 7/transmembrane adapter protein 3 (Prr7) down-regulation in dendrites of rat hippocampal neurons is necessary for homeostatic synaptic depression (HSD) in excitatory neuronsinduced by chronic increase in network activity resulting from a blockade of inhibitory synaptic transmission by picrotoxin (PTX) (Inouye et al. 2022). The small regulatory RNAs, 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, a novel HSD mechanism is revealed in which chronic activity leads to miR-329- and miR-495-mediated Prr7 reduction, upstream of the CDK5-SPAR pathway.