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Abstract Details

Widespread Neuroanatomical Integration and Distinct Electrophysiological Properties of Glioma-innervating Neurons
Neuro-oncology
P4 - Poster Session 4 (5:00 PM-6:00 PM)
6-002
N/A
Gliomas are the most common malignant primary brain tumors and are often associated with severe neurological deficits and mortality. Unlike many cancers, gliomas rarely metastasize outside the brain, indicating a possible dependency on unique features of brain microenvironment. Synapses between neurons and glioma cells exist, suggesting that glioma cells rely on neuronal inputs and synaptic signaling for proliferation. Yet, the locations and properties of neurons that innervate gliomas have remained elusive.
In this study, we utilized transsynaptic tracing with a EnvA-pseudotyped, glycoprotein-deleted rabies virus to specifically infect TVA and glycoprotein-expressing human glioblastoma cells in an orthotopic xenograft mouse model, allowing us to identify the neurons that form synapses onto the gliomas.
Comprehensive whole-brain mapping revealed that these glioma-innervating neurons (GINs) consistently arise at brain regions, including diverse neuromodulatory centers and specific cortical layers, known to project to the glioma locations. Molecular profiling revealed that these long-range cortical GINs are predominantly glutamatergic, and subsets express both glutamatergic and GABAergic markers, whereas local striatal GINs are largely GABAergic. Electrophysiological studies demonstrated that while GINs share passive intrinsic properties with cortex-innervating neurons, their action potential waveforms are altered.
Our study introduces a novel method for identifying and mapping GINs and reveals their consistent integration into existing location-dependent neuronal networks involving diverse neurotransmitters and neuromodulators. The observed intrinsic electrophysiological differences in GINs lay the groundwork for future investigations into how these alterations may correspond with the postsynaptic characteristics of glioma cells.
Authors/Disclosures
Annie L. Hsieh, MD, PhD (Massachusetts General Hospital)
PRESENTER 		An immediate family member of Dr. Hsieh has received personal compensation for serving as an employee of Pfizer.
Sanika Ganesh Ms. Ganesh has received research support from National Science Foundation. Ms. Ganesh has received research support from Harvard University Herchel Smith Fund.
Tomasz Kula, PhD Dr. Kula has received intellectual property interests from a discovery or technology relating to health care.
Madiha Irshad, N/A Ms. Irshad has nothing to disclose.
Emily A. Ferenczi, MD, PhD (Massachusetts General Hospital, Brigham, Harvard) An immediate family member of Dr. Ferenczi has received personal compensation for serving as an employee of Cognito Therapeutics. An immediate family member of Dr. Ferenczi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cognito Therapeutics. An immediate family member of Dr. Ferenczi has stock in Cognito Therapeutics. Dr. Ferenczi has stock in MapLight Therapeutics. The institution of Dr. Ferenczi has received research support from NIH. The institution of Dr. Ferenczi has received research support from Burroughs Wellcome Fund. Dr. Ferenczi has received intellectual property interests from a discovery or technology relating to health care. Dr. Ferenczi has received publishing royalties from a publication relating to health care.
Wengang Wang, MD Dr. Wang has nothing to disclose.
Yi-Ching Chen, BS Miss Chen has nothing to disclose.
Songhua Hu, PhD Dr. Hu has nothing to disclose.
Zongyu Li, PhD Dr. Li has nothing to disclose.
shakchhi joshi Ms. joshi has nothing to disclose.
Marcia Haigis, PhD Dr. Haigis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ReFuel Bio. Dr. Haigis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alixia. Dr. Haigis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MitoQ. Dr. Haigis has received research support from ReFuel Bio. Dr. Haigis has received personal compensation in the range of $5,000-$9,999 for serving as a Advisor with Allison Institute.
Bernardo L. Sabatini, MD, PhD Dr. Sabatini has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neumora. Dr. Sabatini has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Sloan Foundation. Dr. Sabatini has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Pershing Square. Dr. Sabatini has stock in Neumora. The institution of Dr. Sabatini has received research support from NIH. The institution of Dr. Sabatini has received research support from HHMI. The institution of Dr. Sabatini has received research support from NLM. The institution of Dr. Sabatini has received research support from NVF.