4 YEAR PhD IN NEUROSCIENCE
The Wolfson Institute for Biomedical Research, UCL Adaptive myelination in learning and memory
We study the development and functions of glial cells (oligodendrocytes and astrocytes) during embryogenesis and adulthood. Oligodendrocytes, the myelin-forming cells of the CNS, insulate axons and are required for rapid conduction of action potentials.
Oligodendrocytes continue to be generated during adulthood from “adult oligodendrocyte precursors” or “NG2 cells” that persist in the adult brain and spinal cord (5% of all neural cells). The adult-born oligodendrocytes generate new myelin in the corpus callosum and other fibre tracts; this would be expected to alter the properties of the late-myelinating axons and their neural circuits, suggesting that myelin might play a more active role in neural plasticity than previously recognized. In this vein, we recently showed that active myelination during adulthood is required for mice to learn a new motor skill (learning to run at speed on a "complex wheel" with unevenly spaced rungs). We are currently examining the cellular dynamics that underpin motor learning. We have found that oligodendrocyte lineage cells are involved in the earliest stages of motor learning (within the first 3 hours). Structural changes to grey and white matter can also be detected within this time frame by MRI imaging but it is not known how the MRI image relates to the cellular or subcellular composition of the tissue.
An example of a rotation project:
1) The student will investigate changes in the cellular structure of the mouse corpus callosum and overlying sensorimotor cortex in response to motor skill learning, by immunolabelling or in situ hybridization with developmental stage-specific markers of the oligodendrocyte lineage, as well as markers of astrocytes and microglia, to determine how these glial elements change at different stages of motor learning from hours to days. In parallel, mouse brains will be sent for MRI scanning (in collaboration with the universities of Oxford and Utrecht) to allow correlations between the histological and MRI images at different times. In parallel, the student will compare the rates of production of new myelinating oligodendrocytes in normally-caged mice and mice in enriched environments with freely-moving or immobilized running wheels, to distinguish the effects of environment versus motor activity on adult myelination. Skills learned: tissue preparation, cryosectioning, immunocytochemistry, confocal microscopy, mouse behavioural testing.
Bergles, D.E. and Richardson, W.D. (2015). Oligodendrocyte development and plasticity. In Glia; Cold Spring Harbor Laboratory Press (Cold Spring Harbor) (eds BA Barres, MR Freeman, B Stevens). pp139-165. (review: PDF available at http://www.ucl.ac.uk/~ucbzwdr/Richardson.htm -> publications)
McKenzie, I.A., Ohayon, D., Li, H., Paes de Faria, J., Emery, B., Tohyama, K. and Richardson, W.D. (2014). Motor skill learning requires active central myelination. Science 346, 318-322.
Young, K.M., Psachoulia, K., Tripathi, R.B., Dunn, S.-J., Cossell, L., Attwell, D., Tohyama, K. and Richardson, W.D. (2013). Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodelling. Neuron 77, 873-885.
Tsai, H.-H., Li, H., .... Richardson, W.D.* and Rowitch, D.H.* (2012). Regional astrocyte allocation regulates CNS synaptogenesis and repair. Science 337, 358-362. * joint senior authors
Li, H., Paes de Faria, J., Andrew, P. Nitarska, J. and Richardson, W.D. (2011). Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch. Neuron 69, 918-929.
Zawadzka, M., Rivers, L., .... *Richardson, W.D. and *Franklin, R.J.M. (2010). CNS-resident glial progenitor/stem cells make Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell 6, 578-590. * joint senior authors
Rivers, L.E., Young, K.M., Rizzi, M., Jamen, F., Psachoulia, K., Wade, A., Kessaris, N. and Richardson, W.D. (2008) PDGFRA/ NG2-positive glia generate myelinating oligodendrocytes and cortical projection neurons in adult mice. Nat. Neurosci. 11, 1392-1401.