Behavioral Testing. Ultimately the goal of promoting regeneration and synaptogenesis is to improve behavioral outcomes. We test the injured animals with a battery of tasks that mainly assess fine motor control in their forelimbs, for example the ability to retrieve food pellets or traverse a horizontal ladder without missing the rungs. We focus on forelimb control for two reasons. First, this is known to be a main function of the corticospinal tract, one of the main types of axons we study in the lab. Second, and more importantly, regaining hand function is a main priority identified by patients with high cervical injury, and these tasks are the best approximation of hand function in rodent models. Our use of these tests is described in more detail in recent publications (Wang et al. 2015, Jayaprakash et al. 2016).
Until very recently, our success in promoting axon regeneration and synapse formation has not been matched by success in promoting functional recovery. We think there are two main reasons for this. First, we probably need more regeneration, and from more types of neurons. Finding improved combinations of genes and improved delivery systems to reach more neurons are one major direction for the lab. Early success in this direction is hinting that we are on the right track. Second, the regenerated axons are likely not optimally targeted, that is, although they are definitely making synaptic connections with spinal neurons, these targets may not be the best for restoring function. Thus monitoring the exact cells that receive the new connections, and sculpting the connectivity with rehabilitation or controlled neural activity, is a second major research direction for the lab.
Ephys/optogenetics