title: Striatal neurones have a specific ability to respond to phasic dopamine release.
abstract: The cAMP/protein kinase A (PKA) signalling cascade is ubiquitous, and each step in this cascade involves enzymes that are expressed in multiple isoforms. We investigated the effects of this diversity on the integration of the pathway in the target cell by comparing prefrontal cortical neurones with striatal neurones which express a very specific set of signalling proteins. The prefrontal cortex and striatum both receive dopaminergic inputs and we analysed the dynamics of the cAMP/PKA signal triggered by dopamine D1 receptors in these two brain structures. Biosensor imaging in mouse brain slice preparations showed profound differences in the D1 response between pyramidal cortical neurones and striatal medium spiny neurones: the cAMP/PKA response was much stronger, faster and longer lasting in striatal neurones than in pyramidal cortical neurones. We identified three molecular determinants underlying these differences: different activities of phosphodiesterases, particularly those of type 4, which strongly damp the cAMP signal in the cortex but not in the striatum; stronger adenylyl cyclase activity in the striatum, generating responses with a faster onset than in the cortex; and DARPP-32, a phosphatase inhibitor which prolongs PKA action in the striatum. Striatal neurones were also highly responsive in terms of gene expression since a single sub-second dopamine stimulation is sufficient to trigger c-Fos expression in the striatum, but not in the cortex. Our data show how specific molecular elements of the cAMP/PKA signalling cascade selectively enable the principal striatal neurones to respond to brief dopamine stimuli, a critical process in incentive learning.
authors.affiliation: Neurobiologie des Processus Adaptatifs UMR7102 CNRS UPMC, F-75005 Paris, France.
authors.forename: Liliana R V
authors.initials: LR
authors.lastname: Castro
authors.forename: Marina
authors.initials: M
authors.lastname: Brito
authors.forename: Elvire
authors.initials: E
authors.lastname: Guiot
authors.forename: Marina
authors.initials: M
authors.lastname: Polito
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Korn
authors.forename: Denis
authors.initials: D
authors.lastname: Hervé
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
authors.forename: Danièle
authors.initials: D
authors.lastname: Paupardin-Tritsch
authors.forename: Pierre
authors.initials: P
authors.lastname: Vincent
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D015374:Biosensing Techniques; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D010726:Phosphodiesterase Inhibitors; C497929:Ppp1r1b protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D005576:Colforsin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine
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