Research

Unlike any other cell in the adult cerebral cortex, new oligodendrocytes are continuously generated from a resident population of progenitors called NG2 glia. 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 a large number of 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 neuropathological conditions.

  • 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 NG2 glia proliferation and oligodendrocyte generation.

We are interested in understanding the transformation that occurs when a single NG2 glial cell decides to proliferate and or differentiate into a myelinating oligodendrocyte. We have developed tools to investigate these processes both in the live animal and in organotypic culture models.

  • 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
NG2 glia 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.

  • Hill RA, Tong L, Yuan P, Murikinati S, Gupta S, and Grutzendler J. (2015) Neuron. PMID: 26119027
  • Hill RA, Damisah EC, Chen F, Kwan AC, and Grutzendler J. (2017) Nature Communications. PMID: 28621306
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