Publication Date
5-27-2024
Journal
Nature Communications
DOI
10.1038/s41467-024-48757-5
PMID
38802334
PMCID
PMC11130179
PubMedCentral® Posted Date
5-27-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Glioblastoma, Animals, Brain Neoplasms, Mice, Humans, Nerve Net, Glutamic Acid, Neurons, Cerebral Cortex, Calcium Signaling, Disease Models, Animal, Male, Calcium, Female, Cancer in the nervous system, CNS cancer, Astrocyte, Cancer microenvironment, CNS cancer
Abstract
The emergence of glioblastoma in cortical tissue initiates early and persistent neural hyperexcitability with signs ranging from mild cognitive impairment to convulsive seizures. The influence of peritumoral synaptic density, expansion dynamics, and spatial contours of excess glutamate upon higher order neuronal network modularity is unknown. We combined cellular and widefield imaging of calcium and glutamate fluorescent reporters in two glioblastoma mouse models with distinct synaptic microenvironments and infiltration profiles. Functional metrics of neural ensembles are dysregulated during tumor invasion depending on the stage of malignant progression and tumor cell proximity. Neural activity is differentially modulated during periods of accelerated and inhibited tumor expansion. Abnormal glutamate accumulation precedes and outpaces the spatial extent of baseline neuronal calcium signaling, indicating these processes are uncoupled in tumor cortex. Distinctive excitability homeostasis patterns and functional connectivity of local and remote neuronal populations support the promise of precision genetic diagnosis and management of this devastating brain disease.
Included in
Mental and Social Health Commons, Neoplasms Commons, Nervous System Diseases Commons, Neurology Commons, Neurosciences Commons, Oncology Commons