Striatal cholinergic interneurons regulate cognitive and affective dysfunction in partially dopamine-depleted mice

Autor: Marianne Amalric, Samira Ztaou, Isabelle Watabe, Juliette Lhost, Giulia Torromino
Přispěvatelé: Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Neurosciences sensorielles et cognitives (NSC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Ztaou, S, Lhost, J, Watabe, I, Torromino, G, Amalric, M., Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: European Journal of Neuroscience
European Journal of Neuroscience, Wiley, 2018, 48 (9), pp.2988-3004. ⟨10.1111/ejn.14153⟩
European Journal of Neuroscience, 2018, 48 (9), pp.2988-3004. ⟨10.1111/ejn.14153⟩
ISSN: 0953-816X
1460-9568
Popis: International audience; Early non-motor symptoms such as mood disorders and cognitive deficits are increasingly recognised in Parkinson's disease (PD). They may precede the characteristic motor symptomatology caused by dopamine (DA) neuronal loss in the substantia nigra pars compacta (SNc). It is well known that striatal cholinergic interneurons (ChIs) are emerging as key regulators of PD motor symptom, however, their involvement in the cognitive and affective alterations occurring in the premotor phase of PD is poorly understood. We used optogenetic photoinhibition of striatal ChIs in mice with mild nigrostriatal 6-hydroxydopamine (6-OHDA) lesions and assessed their role in anxiety-like behaviour in the elevated plus maze, social memory recognition of a congener and visuospatial object recognition. In transgenic mice specifically expressing halorhodopsin (eNpHR) in cholinergic neurons, striatal ChIs photoinhibi-tion reduced the anxiety-like behaviour and reversed social and spatial short-term memory impairment induced by moderate DA depletion (e.g., 50% loss of tyrosine hydroxylase TH-positive neurons in the SNc). Systemic injection of telenzepine (0.3 mg/kg), a preferential M1 muscarinic cholinergic receptors antagonist, improved anxiety-like behaviour, social memory recognition but not spatial memory deficits. Our results suggest that dysfunction of the striatal cholinergic system may play a role in the short-term cognitive and emotional deficits of partially DA-depleted mice. Blocking cholinergic activity with M1 muscarinic receptor antagonists may represent a possible therapeutic target, although not exclusive, to modulate these early non-motor deficits.
Databáze: OpenAIRE
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