title: Homer 1a and mGluR5 phosphorylation in reward-sensitive metaplasticity: A hypothesis of neuronal selection and bidirectional synaptic plasticity.
abstract: 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.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: tanya.marton@gmail.com.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Marton
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: shuler@jhmi.edu.
authors.forename: Marshall G
authors.initials: MG
authors.lastname: Hussain Shuler
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: pworley@jhmi.edu.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D000072233:Homer Scaffolding Proteins; D006801:Humans; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012201:Reward; D013569:Synapses / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D064529:Receptor, Metabotropic Glutamate 5
keywords: Addiction; Dopamine; Eligibility trace; Homer; Immediate early gene; NMDA receptor; Neuronal selection; PIN1; Protoweight; Provisional weight; Reinforcement learning; Reward learning; Synaptic plasticity; Synaptic tag; mGluR5