Interplay between inhibitory control and behavioural flexibility: impact of dorsomedial striatal dopamine denervation in mice

Autor: Didier Louber, Juliette Lhost, Simon Moré, Martine Liberge, Abdel-Mouttalib Ouagazzal, Isabelle Watabe, Marianne Amalric
Přispěvatelé: Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2021
Předmět:
Zdroj: Neuroscience
Neuroscience, Elsevier-International Brain Research Organization, 2021, 477, pp.25-39. ⟨10.1016/j.neuroscience.2021.09.026⟩
Neuroscience, 2021, 477, pp.25-39. ⟨10.1016/j.neuroscience.2021.09.026⟩
ISSN: 2267-828X
0306-4522
1873-7544
DOI: 10.1016/j.neuroscience.2021.09.026
Popis: International audience; In Parkinson's disease, nigrostriatal dopamine (DA) degeneration is commonly associated with motor symptomatology. However, non-motor symptoms affecting cognitive function, such as behavioural flexibility and inhibitory control may also appear early in the disease. Here we addressed the role of DA innervation of the dorsomedial striatum (DMS) in mediating these functions in 6-hydroxydopamine (6-OHDA)-lesioned mice using instrumental conditioning in various tasks. Behavioural flexibility was studied in a simple reversal task (nosepoke discrimination) or in reversal of a two-step sequence of actions (central followed by lateral nose-poke). Our results show that mild DA lesions of the DMS induces behavioural flexibility deficits in the sequential reversal learning only. In the first sessions following reversal of contingency, lesioned mice enhanced perseverative sequence of actions to the initial rewarded side then produced premature responses directly to the correct side omitting the central response, thus disrupting the two-step sequence of actions. These deficits may be linked to increased impulsivity as 6-OHDA-lesioned mice were unable to inhibit a previously learned motor response in a cued response inhibition task assessing proactive inhibitory control. Our findings show that partial DA denervation restricted to DMS impairs behavioural flexibility and proactive response inhibition in mice. Such striatal DA lesion may thus represent a valuable animal model for exploring deficits in executive control documented in early stage of Parkinson's disease.
Databáze: OpenAIRE
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