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

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 rnetabotropic glutamate receptor 5 (mGluR5)'s Homer ligand, and the enhancement of an NMDA receptor-dependent current. Inspired by hypotheses that Homer la functions selectively in recently-active synapses, we propose that Homer la is recruited by a synaptic tag to functionally discriminate between synapses that predict reward and those that do not. The involvement of Homer la 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. (C) 2015 Published by Elsevier B.V.