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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Investigation of the function of nigrostriatal dopaminergic neurons in motivated behaviors with DREADDs

Objectifs

Understand the implication of the dopaminergic nigrostriatal system in non motor functions and in the pathophysiology of neuropsychiatric symptoms related to Parkinson’s disease (PD), with the selective manipulation of this system in vivo with DREADDs.

Résumé

PD is a neurodegenerative disorder characterized by motor symptoms. However, PD is also associated with a plethora of neuropsychiatric and cognitive impairments, including apathy (a severe deficit in motivation), depression and anxiety.
Previous studies from the laboratory evidenced a major role of the dopaminergic nigrostriatal system in the pathophysiology of such emotional and motivational deficits related to PD.
In order to further investigate the implication of this system in motivational and emotional functions, we will use a DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) approach in transgenic rats to selectively manipulate dopaminergic neurons in vivo.

Méthodes

This project with combined in situ infusion of viral vectors, behavioral evaluation of rodents and immunohistochemistry and imaging (fluorescent microscopy approaches).

Références

  • Magnard R*, Vachez Y*, Carcenac C, Krack P, David O, Savasta M, Boulet S*, Carnicella S* (2016) What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson's disease? Transl Psychiatry 6:e753
  • Favier M, Duran T, Drui G, Carcenac C, Savasta M, Carnicella S (2014) Full reversion of motivational deficits by pramipexole in a rodent model of Parkinson’s disease. Mov Disord 7:912-20
  • Drui G*, Carnicella S*, Carcenac C, Favier M, Bertrand A, Boulet S, Savasta M (2014) Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson's disease. Molecular Psychiatry 19(3):358-67

Contacts

Sébastien Carnicella, CR1 Inserm
Email : sebastien.carnicella@inserm.fr

Mise à jour le 28 mai 2017

Contacts

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