Hyperexcitability in Cultured Cortical Neuron Networks from the G93A-SOD1 Amyotrophic Lateral Sclerosis Model Mouse and its Molecular Correlates

Publication date: Available online 7 August 2019Source: NeuroscienceAuthor(s): Stefania Marcuzzo, Benedetta Terragni, Silvia Bonanno, Davide Isaia, Paola Cavalcante, Cristina Cappelletti, Emilio Ciusani, Ambra Rizzo, Giulia Regalia, Natsue Yoshimura, Giovanni Stefano Ugolini, Marco Rasponi, Giulia Bechi, Massimo Mantegazza, Renato Mantegazza, Pia Bernasconi, Ludovico MinatiAbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the corticospinal tract and leading to motor neuron death. According to a recent study, magnetic resonance imaging-visible changes suggestive of neurodegeneration seem absent in the motor cortex of G93A-SOD1 ALS mice. However, it has not yet been ascertained whether the cortical neural activity is intact, or alterations are present, perhaps even from an early stage. Here, cortical neurons from this model were isolated at post-natal day 1 and cultured on multielectrode arrays. Their activity was studied with a comprehensive pool of neurophysiological analyses probing excitability, criticality and network architecture, alongside immunocytochemistry and molecular investigations. Significant hyperexcitability was visible through increased network firing rate and bursting, whereas topological changes in the synchronization patterns were apparently absent. The number of dendritic spines was increased, accompanied by elevated transcriptional levels of the DLG4 gene, NMDA receptor 1 and the early pro-apoptotic APAF1 gene. The extra...
Source: Neuroscience - Category: Neuroscience Source Type: research