Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.
BMC Biol
; 18(1): 58, 2020 05 28.
Article
en En
| MEDLINE
| ID: mdl-32466798
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Huntington
/
Cuerpo Estriado
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
BMC Biol
Asunto de la revista:
BIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
España