Michelle Monje, MD, PhD

Professor of Neurology and Neurological Sciences Investigator

Howard Hughes Medical Institute

Stanford University

Host(s): Swarnali Acharyya (Faculty)

Neuron-glial interactions in health and disease: from cognition to cancer

In the central nervous system, neuronal activity is a critical regulator of development and plasticity. Activity-dependent proliferation of healthy glial progenitors, oligodendrocyte precursor cells (OPCs), and the consequent generation of new oligodendrocytes contributes to adaptive myelination. This plasticity of myelin tunes neural circuit function and contributes to healthy cognition, while disruption of myelin plasticity contributes to cognitive impairment in a range of disease states. The robust mitogenic effect of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, suggests that dysregulated or “hijacked” mechanisms of myelin plasticity might similarly promote malignant cell proliferation in this devastating group of brain cancers. Indeed, neuronal activity promotes progression of both high-grade and low-grade glioma subtypes in preclinical models. Crucial mechanisms mediating activity-regulated glioma growth include paracrine secretion of tumor-promoting factors and synaptic communication between neurons and glioma cells. Glioma cells integrate into neural circuits synaptically through neuron-to-glioma synapses that exhibit synaptic plasticity, and electrically through potassium-evoked currents that are amplified via gap-junctional coupling between tumor cells. This synaptic and electrical integration of glioma into neural circuits is central to tumor progression in preclinical models. Thus, neuron-glial interactions not only modulate neural circuit structure and function in the healthy brain, but neuron-glioma interactions also play important roles in the pathogenesis of glial cancers. The mechanistic parallels between normal and malignant neuron-glial interactions underscores the extent to which mechanisms of neurodevelopment and plasticity are subverted by malignant gliomas, and the importance of understanding the neuroscience of cancer.

Relevant Publications:

Loss of Adaptive Myelination Contributes to Methotrexate Chemotherapy-Related Cognitive Impairment

Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain

Tuesdays@10 is a signature Zuckerman Institute initiative that aims to expose researchers at all levels to high-quality science and stimulate scientific discourse. The speakers featured in this series represent various fields and techniques in neuroscience, and include invited guests of the Columbia Neuroscience Seminars, the Zuckerman Institute's Local Circuits Affiliates Program, and other special seminar series through a combined, collaborative effort of one or more of the following: Columbia's Zuckerman Institute, the Center for Precision Psychiatry, the Center for Theoretical Neuroscience, the Department of Neuroscience, the Doctoral Program in Neurobiology and Behavior and the Columbia Translational Neuroscience Initiative, and with support from the Kavli Institute for Brain Science. 

More information and a full schedule can be found here.