Latest Developments in the Lab
An interactive atlas of supraspinal input! In a collaborative project with Dr. Pantelis Tsoulfas at the University of Miami, we are constructing a community resource to answer some hard questions in the SCI field. We know in general terms that many different types of neurons project axons to the spinal cord, but exactly how many exist and where exactly are they located? More importantly, to what extent does each population of axons survive any given injury? Which types of axons are responding to our pro-regenerative treatments - and which ones aren't? The starting point for all these questions is a means to identify neurons that project axons to different spinal levels, to register them to 3D atlases, and to count them in the presence or absence of graded injury. You can explore a beta version of this resource at 3dmousebrain.com. Feedback is appreciated!
Retrograde gene delivery. A major limit to gene therapy for spinal injury is the current practice of injecting virus directly to the brain. It is fine for proof-of-principle work, but puts a low ceiling on the functional gains we can hope to see even in a rodent, let alone a patient. The problem is that there are too many supraspinal neurons in too many locations - it's impossible to hit them all. As many researchers are aware, the solution is a retrograde approach, in which vectors are delivered to spinal tracts (a small target) and then spread back to cell bodies of origin throughout the brain. Now, with a new vector developed at Janelia, it looks like this idea can become a practical reality. We have systematically tested injecting Retro-AAV to the spinal cord, both uninjured and after cervical transection, and find spectacular efficiency in supraspinal populations including the major players (corticospinal, rubrospinal, vestibulospinal, and reticulospinal). Other tracts that we don't tend to think about are also transduced, for instance hypothalamospinal tracts and cerebellar spinal tracts. To illustrate the point we collaborated with Dr. Pantelis at the Miami Project, who performed tissue clearing and 3D imaging of mouse brains after cervical injection of Retro-AAV-tdTomato. In the videos below you can appreciate how the virus reaches a broad range of supraspinal neurons. Check out our recent pre-print for more details.