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Article Dans Une Revue The Journal of Physiology Année : 2013

Striatal neurones have a specific ability to respond to phasic dopamine release

Marina Brito
  • Fonction : Auteur
Elvire Guiot
  • Fonction : Auteur
Marina Polito
  • Fonction : Auteur
Christoph W. Korn
  • Fonction : Auteur
Denis Herve
  • Fonction : Auteur
Jean-Antoine Girault
Daniele Paupardin-Tritsch
  • Fonction : Auteur

Résumé

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 D-1 receptors in these two brain structures. Biosensor imaging in mouse brain slice preparations showed profound differences in the D-1 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.

Dates et versions

hal-01545404 , version 1 (22-06-2017)

Identifiants

Citer

Liliana R. V. Castro, Marina Brito, Elvire Guiot, Marina Polito, Christoph W. Korn, et al.. Striatal neurones have a specific ability to respond to phasic dopamine release. The Journal of Physiology, 2013, 591 (13), pp.3197-3214. ⟨10.1113/jphysiol.2013.252197⟩. ⟨hal-01545404⟩
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