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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Home > Research > Research teams > Physiopathology of Motivation (Sébastien CARNICELLA)

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Team "Physiopathology of Motivation" *

Manager: Sébastien CARNICELLA

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The major aim of our group is to uncover the physiopathological mechanisms underlying the development of neuropsychiatric symptoms in neurological disorders such as Parkinson’s disease (PD).

Research themes and techniques used

Beyond the cardinal motor features of the disease, PD is indeed associated with a plethora of behavioral complications ranging from apathy (defined as a loss of motivation), anhedonia, depression and anxiety to an heterogeneous group of impulsive-compulsive behaviors (including pathological gambling, hypersexuality, …) that resembles addiction in terms of phenomenology and putative psychobiological mechanisms.

This cluster of symptoms, which was largely neglected in the past, severely impairs patients’ quality of life and is now recognized as a major contributor to morbidity. However, their underlying neurobiological and cellular mechanisms remain unclear, as well as the influence on these symptoms of the gold-standard pharmacological and neurosurgical treatments of the disease, namely dopamine replacement therapies (DRTs) and deep brain stimulation of the subthalamic nucleus (STN-DBS).

In a multidisciplinary and translational strategy, we address these questions through two main research projects:

  • Pathophysiology of apathy, depression and impulsive-compulsive behaviors in PD: investigating with a rodent model of non-motor symptoms of PD developed in the laboratory and experimental deep brain stimulation the implication of nigrostriatal dopamine and corticostriatal circuits dysfunctions in abnormal motivational and impulsive behaviors. Evaluating the therapeutic and side effects of DRTs on such behaviors in rats and humans.

  • Identification of transcriptomic and metabolomic markers of PD-related neuropsychiatric symptoms: psychiatric and neurodegenerative disorders are accompanied with profound modifications of the expression of microRNAs (small non-coding RNA sequences that powerfully regulate the translation of mRNAs) and metabolites. In a collaborative and translational project with Barbier’s team, the clinical transcriptomic facility and the Movement Disorder Unit of the Grenoble University Hospital, analyzing microRNAs and metabolites levels in in specific brain regions (rats) and blood samples (rats and patients) to identify specific markers of apathy and impulsive-compulsive behaviors, in order to develop innovative predictive medical tools and therapeutic approaches.

Expertise and techniques

  • Animal behavior: evaluation of mood-related, Pavlovian, operant and motor behaviors.

  • Experimental deep brain stimulation: implantable microstimulators for chronic and long-term stimulation in freely-moving rats.

  • Histology and neuroanatomy: immunohistochemistry, autoradiography, immunofluorescence, optical microscopy.

  • Neurochemistry and neuropharmacology: microdialysis in vivo, HPLC (catecholamines), stereotaxic surgery.
     

Publications

What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson’s disease?. Magnard R, Vachez Y, Carcenac C, Krack P, David O, Savasta M, Boulet S, Carnicella S (in press). Transl Psychiatry.

Subthalamic deep brain stimulation differently alters striatal dopaminergic receptor levels in rats. Carcenac C, Favier M, Vachez Y, Lacombe E, Carnicella S, Savasta M, Boulet S (2015). Mov Disord. 30(13):1739-49.

Implication of dopamine D3 receptor activation in the reversion of Parkinson's disease-related motivational deficits. Carnicella S, Drui G, Boulet S, Carcenac C, Favier M, Duran T, Savasta M (2014). Transl Psychiatry. 17;4:e401.

Pramipexole reverses Parkinson's disease-related motivational deficits in rats. Favier M, Duran T, Carcenac C, Drui G, Savasta M, Carnicella S (2014). Mov Disord. 29(7):912-20.

Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson's disease. Drui G, Carnicella S, Carcenac C, Favier M, Bertrand A, Boulet S, Savasta M (2014). Mol Psychiatry. 19(3):358-67.


Updated on September 20, 2018

Keywords

Dopamine, Parkinson’s disease, deep brain stimulation, psychiatry, addictions, animal behavior, translational

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