A central goal of the Hébert Lab is to reconstruct neocortical tissue in such a way that the activity of this new tissue can encode useful behavior to the animal. One strategy for approaching this goal is by combining a normal complement of neocortical cell types for transplantation, including neuronal, glial, and vascular subtypes, and arranging the cells in a laminar cytoarchitecture that resembles the normal neocortex.

A human neocortical neuron 2 days after transplantation into the adult mouse neocortex. Note growth cone finding its way.

Within 2 weeks after transplantation, neuronal projections have crossed cerebral hemispheres via the corpus callosum (left) and descended to innervate the striatum (right).
If vascular endothelial cells are included in the transplant cell population, they form vessels (green) and integrate with the host vasculature.
Human vascular endothelial cells (30 days after transplantation with neuronal stem cells) have formed extensive vessels within the graft (2-photon live imaging).
One way to visualize blood circulation in live animals is to label a small fraction of erythrocytes with DiO (rapidly moving green dots).
A key aspect to obtaining functional cortical tissue is cytoarchitecture. To minimize experimental variability, we standardize the size of neocortical lesions with the aim of optimizing the deposition of a structured cellularized bioscaffold.
Another goal of the Hébert Lab is to use microglia as a vehicle for the long-term and widespread delivery of biologics or cells to the neocortex.
The lab has developed a protocol that allows for a single injection of engineered microglia to result in the distribution of these cells throughout large areas of cortex.
A potential application for microglia dispersion in the cortex that is being explored is the replacement of neurons in age-related degeneration via direct conversion of engineered microglia to neocortical neurons.