Research

Unlike any other cell in the adult cerebral cortex, new oligodendrocytes are continuously generated from a resident population of oligodendrocyte progenitor cells (OPCs). Oligodendrocytes generated via this process make myelin, a critical component for the establishment and maintenance of mature neural networks. Disruption in the process of oligodendrocyte generation and homeostatic maintenance of myelin throughout life is likely involved in many neurological disorders in addition to debilitating demyelinating diseases such as multiple sclerosis. Many questions remain about how oligodendrocytes establish elaborate compact myelin-forming internodes, how stable these structures are, and how communication between the axon and oligodendrocyte modulates this process. Understanding these processes has broad implications for mechanisms of neural network homeostasis and disruption in disease.

1) Mechanisms of long-term myelin plasticity and pathology.

We have developed a comprehensive set of tools for live label-free and fluorescence-based imaging of myelin and oligodendrocyte gap junction coupling with astrocytes. These techniques allow us to investigate the formation, plasticity, and regeneration of these structures over time and in various experimental conditions. Furthermore, these approaches can be applied to multiple disease models in order to understand how and why different cells and subcellular structures are disrupted in numerous pathological conditions.

  • Chapman TW, Olveda G, Bame Xh, Pereira E, and Hill RA. (2023) Nature Neuroscience. PMID: 36928635
  • Hill RA, Li AM, and Grutzendler J. (2018) Nature Neuroscience. PMID: 29556031
  • Hill RA and Grutzendler J. (2014) Nature Methods. PMID: 25357236
  • Schain AJ, Hill RA, and Grutzendler J. (2014) Nature Medicine. PMID: 24681598
imaging approaches for detecting myelin plasticity
long-term changes in cortical myelination

2) Cellular and molecular mechanisms of OPC proliferation and oligodendrocyte generation.

We are interested in understanding the transformation that occurs when a single OPC decides to proliferate and or differentiate into a myelinating oligodendrocyte. We have developed tools to investigate these processes in the live animal and organotypic culture models.

  • Bame X and Hill RA. (2024) Nature Communications. PMID: 39143079
  • Chapman TW, Olveda G, Bame Xh, Pereira E, and Hill RA. (2023) Nature Neuroscience. PMID: 36928635
  • Hill RA, Patel KD, Goncalves CM, Grutzendler J, and Nishiyama A. (2014) Nature Neuroscience, PMID: 25262495
  • Hill RA, Patel KD, Medved J, Reiss AM, and Nishiyama A. (2013) The Journal of Neuroscience. PMID: 24005306
OPCs imaged over 26 days in the live brain

3) Neuron-glia interactions in the brain.

Research topics include neurovascular coupling and mechanisms and consequences of single-cell death in the live brain.

  • Olveda GE, Barasa MN, and Hill RA. (2024) Cell Reports. PMID: 38935500
  • Hill RA, Damisah EC, Chen F, Kwan AC, and Grutzendler J. (2017) Nature Communications. PMID: 28621306
  • Hill RA, Tong L, Yuan P, Murikinati S, Gupta S, and Grutzendler J. (2015) Neuron. PMID: 26119027
visualizing the neurovascular unit in the live brain
targeted 2-photon ablation (2Phatal) of single neurons

For more information see our publications

Biological Sciences
Dartmouth College
Hanover, NH 03755