Glioblastoma disrupts cortical network activity at multiple spatial and temporal scales

Area of Science:

• Neuroscience
• Oncology
• Systems Biology

Background:

• Glioblastoma triggers neural hyperexcitability, leading to symptoms like seizures.
• The impact of tumor characteristics on neuronal network function remains unclear.

Purpose of the Study:

• To investigate how glioblastoma affects neuronal network modularity.
• To explore the relationship between tumor progression, glutamate levels, and neural activity.

Main Methods:

• Utilized cellular and widefield imaging in two glioblastoma mouse models.
• Employed calcium and glutamate fluorescent reporters to monitor neural activity.
• Analyzed functional metrics of neural ensembles in relation to tumor invasion.

Main Results:

• Neural ensemble activity is dysregulated by tumor invasion, varying with progression stage and proximity.
• Abnormal glutamate accumulation precedes and exceeds neuronal calcium signaling, indicating uncoupling.
• Distinct patterns of excitability and connectivity were observed in local and remote neuronal populations.

Conclusions:

• Tumor-induced neural hyperexcitability is complex and stage-dependent.
• Glutamate dysregulation is an early event in glioblastoma's impact on neural function.
• Findings support precision diagnostics and management strategies for glioblastoma.