Forelimb reach task
The effects of motor learning on cortical oligodendrogenesis in health & disease
How does activity-dependent myelination shape the adult brain? We teach mice to perform a forelimb reach task to observe how motor learning shapes oligodendrocyte lineage cells and myelination in the forelimb region of motor cortex using longitudinal in vivo two-photon imaging. Our current findings indicate learning transiently suppresses oligodendrocyte precursor cell (OPC) proliferation and oligodendrocyte generation, and subsequently increases both OPC differentiation and oligodendrocyte generation. We also found that the learning-induced burst of oligodendrogenesis can be used to promote remyelination after demyelinating injury.
The effects of myelin loss on cortical neuronal activity
We are investigating the effects of myelin loss on motor cortex circuit function in awake, behaving mice. We use both chronically implanted NeuroNexus and acutely implanted Neuropixel extracellular recording arrays in mice throughout demyelination and remyelination to study single-cell activity changes. We have shown that myelin loss causes neuronal hyperexcitability that recovers with partial remyelination. This project is in collaboration with the laboratories of Cristin Welle and Dan Denman at the University of Colorado.
Developing new in vivo models of demyelination
We are testing a new in vivo model of focal cortical demyelination using recombinant antibodies derived from Multiple Sclerosis patients to cause immune-mediated lesions. We use longitudinal in vivo two-photon imaging and single-cell RNA sequencing to characterize the complex dynamics between cortical oligodendrocyte lineage cells and microglia throughout antibody-mediated demyelination. This project is part of a consortium at the University of Colorado with the laboratories of Jeffrey Bennett, Greg Owens, and Wendy Macklin.
Surviving oligodendrocytes: a new frontier in remyelination
We recently discovered a new cell type that participates in remyelination: mature, myelinating oligodendrocytes that survive demyelination. We are now investigating how these cells are stimulated to participate in remyelination and to what extent they contribute to restoring baseline myelination pattern .
Cortical volume imaged with 3-photon system
In vivo three-photon microscopy of the cortical gray and white matter
Our lab routinely uses in vivo 2-photon imaging to track the behavior of oligodendrocyte lineage cells in the living brain. However, due to scattering of the excitation light, this technique is limited to the superficial layers of the mouse cortex. To overcome this limitation, we have partnered with CU Neurophotonics and the lab of Emily Gibson to build a custom 3-photon microscope that enables deep structural imaging to >1000 um depths in the intact mouse brain. We have characterized this technique extensively and are using the technology to ask questions related to gray and white matter differences in healthy adult oligodendrogenesis and myelin regeneration following demyelinating disease.