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

The European Journal of Neuroscience
Samira ZtaouMarianne Amalric

Abstract

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 photoinhibition 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 behavio...Continue Reading

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Citations

Apr 12, 2019·Biomolecules·Fabio Del BelloWilma Quaglia
Apr 18, 2020·The European Journal of Neuroscience·Cecilia Tubert, Mario Gustavo Murer
May 13, 2020·The European Journal of Neuroscience·Ivan Castela, Ledia F Hernandez
Apr 2, 2019·Frontiers in Neural Circuits·Yijuan Du, Steven M Graves
Jan 11, 2020·Frontiers in Pharmacology·Nicolas MalletCorinne Beurrier
Dec 18, 2020·Frontiers in Aging Neuroscience·Sandra BaezAdolfo M García
May 29, 2021·Neuroscience·Rodrigo Manuel Paz, Mario Gustavo Murer
Aug 10, 2021·Frontiers in Behavioral Neuroscience·Marianne AmalricGiovanna Paolone
Sep 4, 2021·Frontiers in Aging Neuroscience·Sumonto MitraJaan-Olle Andressoo

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