ReviewHomer 1a and mGluR5 phosphorylation in reward-sensitive metaplasticity: A hypothesis of neuronal selection and bidirectional synaptic plasticity

•Homer 1a allows PIN1 to isomerize phosphorylated mGluR5, enhancing NMDAR current.•Homer 1a and phospho-mGluR5 allow dopamine to facilitate synaptic potentiation.•Hypothesis: Homer 1a potentiates synapses predicting reward, depresses others.•Hypothesis: some plasticity is restricted to neurons with decaminutes-old firing.•These restrictions may influence which features are encoded in reward memories.

Drug addiction and reward learning both involve mechanisms in which reinforcing neuromodulators participate in changing synaptic strength. For example, dopamine receptor activation modulates corticostriatal plasticity through a mechanism involving the induction of the immediate early gene Homer 1a, the phosphorylation of metabotropic glutamate receptor 5 (mGluR5)′s Homer ligand, and the enhancement of an NMDA receptor-dependent current. Inspired by hypotheses that Homer 1a functions selectively in recently-active synapses, we propose that Homer 1a is recruited by a synaptic tag to functionally discriminate between synapses that predict reward and those that do not. The involvement of Homer 1a in this mechanism further suggests that decaminutes-old firing patterns can define which synapses encode new information.This article is part of a Special Issue entitled SI:Addiction circuits.