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Title: Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
Author: Fernández García, Sara
Orlandi, Javier G.
García-Díaz Barriga, Gerardo
Rodríguez Allué, Manuel José
Masana Nadal, Mercè
Soriano i Fradera, Jordi
Alberch i Vié, Jordi
Keywords: Corea de Huntington
Xarxes neuronals (Neurobiologia)
Huntington's chorea
Neural networks (Neurobiology)
Issue Date: 28-May-2020
Publisher: BioMed Central
Abstract: Background. Network alterations underlying neurodegenerative diseases often precede symptoms and functional deficits. Thus, their early identification is central for improved prognosis. In Huntington's disease (HD), the cortico-striatal networks, involved in motor function processing, are the most compromised neural substrate. However, whether the network alterations are intrinsic of the striatum or the cortex is not fully understood. Results In order to identify early HD neural deficits, we characterized neuronal ensemble calcium activity and network topology of HD striatal and cortical cultures. We used large-scale calcium imaging combined with activity-based network inference analysis. We extracted collective activity events and inferred the topology of the neuronal network in cortical and striatal primary cultures from wild-type and R6/1 mouse model of HD. Striatal, but not cortical, HD networks displayed lower activity and a lessened ability to integrate information. GABAA receptor blockade in healthy and HD striatal cultures generated similar coordinated ensemble activity and network topology, highlighting that the excitatory component of striatal system is spared in HD. Conversely, NMDA receptor activation increased individual neuronal activity while coordinated activity became highly variable and undefined. Interestingly, by boosting NMDA activity, we rectified striatal HD network alterations. Conclusions. Overall, our integrative approach highlights striatal defective network integration capacity as a major contributor of basal ganglia dysfunction in HD and suggests that increased excitatory drive may serve as a potential intervention. In addition, our work provides a valuable tool to evaluate in vitro network recovery after treatment intervention in basal ganglia disorders.
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It is part of: Bmc Biology, 2020, vol. 18, p. 58
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ISSN: 1741-7007
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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