Biology subjects

Olshausen, N.

Publications and source records attributed to Olshausen, N..

3 recordsLinked to original sources

bioRxiv2026

Collective cancer cell calcium activity drives brain metastasis

Communication in multicellular networks is a cancer-intrinsic neural feature and crucial for primary brain tumor growth and resistance, but it is unclear whether brain metastases (BrM), the most common and deadliest brain malignancy, are also driven by communicating cancer networks. Using intravital two-photon microscopy in awake mice, clinical specimens, and Ca2+ integrators, we demonstrate that brain-colonizing breast and lung cancer and melanoma cells display gap-junction-dependent, coordinated Ca2+ activity in multicellular, cancer-cell intrinsic networks, which drives their proliferation. Mechanistically, Ca2+ oscillations induce transcription of immediate early genes, adoption of a neuronal expression profile, and cell cycle progression. While many of those features are enriched in BrM, all investigated cancer cell lines showed collective Ca2+ activity. Therapeutically, blocking Ca2+ activity with gap junction inhibitors reduces BrM burden in mouse models. Here we show communicating cancer cell syncytia as drivers of BrM growth, pointing to a targetable pathomechanism, and potentially a new pan-cancer hallmark. Graphical AbstractIn brief Brain metastases form gap-junction-coupled networks exhibiting spontaneous, coordinated Ca2+ activity linked to immediate early gene activation, neuronal gene programs, and cell cycle progression. Disrupting Ca2+ network communication with gap junction inhibitors induces cell cycle arrest and reduces brain metastatic burden in vivo. O_FIG O_LINKSMALLFIG WIDTH=195 HEIGHT=200 SRC="FIGDIR/small/723715v1_ufig1.gif" ALT="Figure 1"> View larger version (88K): org.highwire.dtl.DTLVardef@1130ea0org.highwire.dtl.DTLVardef@254dcdorg.highwire.dtl.DTLVardef@117021forg.highwire.dtl.DTLVardef@18c4f1e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIBrain metastases display collective Ca2+ activity in gap-junction-coupled networks C_LIO_LICa2+ co-activity is conserved across cancers but enriched in brain metastasis C_LIO_LICa2+ oscillations robustly induce neuronal gene programs and cell cycle progression C_LIO_LIGap junction inhibition reduces brain metastasis burden in mice C_LI

cancer biology↗

bioRxiv2025

Electrocorticographic Detection of Speech Networks in Glioma-infiltrated Cortex

Direct cortical stimulation (DCS) is the clinical gold standard for identifying functional cortex in the human brain, which is essential for the safe removal of brain lesions. Defining the electro-physiological properties of DCS- positive cortical regions may facilitate the identification of critical language regions, thereby permitting safe glioma resections in communities without access. Leveraging a multicenter electrophysiologic dataset of DCS- positive language regions spatially matched with subdural arrays, we analyzed regions identified as functionally critical (DCS+) versus functionally non-critical (DCS-) during intraoperative language mapping. In IDH-mutant gliomas, DCS+ regions exhibited significantly greater speech-related neural activity and enhanced encoding and decoding of linguistic and semantic features. We demonstrate that resting-state classifiers distinguish DCS+ from DCS- regions in IDH-mutant tumors. Task-based and resting-state electrophysiologic distinctions were pathology-specific and not present in IDH-wildtype glioblastomas. These findings may accelerate DCS mapping by guiding surgeons to priority regions, improving efficiency, and patient outcomes.

neuroscience↗

bioRxiv2025

Aperiodic neural dynamics define a novel signature of glioma-induced excitation-inhibition dysregulation

Diffuse gliomas remodel neuronal circuits with prognostic and therapeutic significance for patients. Electrophysiologic measures of cortical excitability hold promise for monitoring disease progression and evaluating therapeutic responses. The power law exponent (aperiodic slope) reflects the balance between excitatory and inhibitory activity within neuronal networks, a critical aspect of normal brain function often disrupted in neurological conditions. Despite its potential, the significance of the aperiodic slope in glioma-infiltrated tissue and its underlying cellular processes has not been fully investigated. Here, we integrate multi-modal electrophysiological analysis with transcriptomic profiling to analyze the aperiodic slope in both normal and glioma-infiltrated cortex. We determine that glioma infiltration induces a flattening of the aperiodic slope, indicating a shift toward excitation dominance that varies according to tumor subtype and correlates with impairments in semantic naming. Single-nucleus RNA sequencing revealed that cortical regions with flat aperiodic slope exhibit transcriptional programs enriched in glutamatergic signaling, membrane depolarization, and excitatory synaptic transmission. The aperiodic slope responds to pharmacologically induced changes in cortical inhibition during propofol administration, a GABAA agonist. Our results establish the aperiodic slope as a robust biomarker of glioma-associated excitation-inhibition imbalance, with potential applications in tumor classification and treatment monitoring.

cancer biology↗