title: Signaling in striatal neurons: the phosphoproteins of reward, addiction, and dyskinesia.
abstract: The striatum is a deep region of the forebrain involved in action selection, control of movement, and motivation. It receives a convergent excitatory glutamate input from the cerebral cortex and the thalamus, controlled by dopamine (DA) released in response to unexpected rewards and other salient stimuli. Striatal function and its dysfunction in drug addiction or Parkinson's disease depend on the interplay between these neurotransmitters. Signaling cascades in striatal medium-sized spiny neurons (MSNs) involve multiple kinases, phosphatases, and phosphoproteins, some of which are highly enriched in these neurons. They control the properties of ion channels and the plasticity of MSNs, in part through their effects on gene transcription. This chapter summarizes signaling in MSNs and focuses on the regulation of multiple protein phosphatases through DA and glutamate receptors and the role of ERK. It is hypothesized that these pathways are particularly adapted to the specific computing properties of MSNs and the function of the basal ganglia circuits in which they participate.
authors.affiliation: Institut du Fer à Moulin, Paris, France.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
mesh_terms: D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D001479:Basal Ganglia / Q000503:physiopathology; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D020935:MAP Kinase Signaling System; D008959:Models, Neurological; D009069:Movement Disorders / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017470:Receptors, Glutamate / Q000378:metabolism; D012201:Reward; D019966:Substance-Related Disorders / Q000503:physiopathology*
chemical_list: D000978:Antiparkinson Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; C497928:PPP1R1B protein, human; D010750:Phosphoproteins; D017470:Receptors, Glutamate; D007980:Levodopa; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine