Discovering ways to discover circuits

 
AAV21.pn
 

For many years, neuroscientists have made use of neurotropic viruses for fluorescent labeling, transgene delivery, as well as tracing of the inputs and outputs of brain areas, neuron populations, or even single neurons.

Prominent examples include a host of natural and engineered viruses and their derivatives such as adeno associated virus (AAVs), rabies virus (RV), vesicular stomatitis virus (VSV), lenti virus (LV), herpes simplex virus (HSV) and many more. This rich toolbox has enabled countless complex experiments and labeling schemes with every virus having its own advantages and drawbacks.

 

An ideal viral tracer (which doesn’t exist yet) would combine the following features:

  •   Show no biased tropism (that is, it would infect all neurons equally)

  •   Cause strong, long-term transgene expression

  •   Non-toxic to cells

  •   Restricted to cells of interest (i.e. via recombinase expression)

  • Can trans-synaptically label synaptically connected neurons in a controlled and unidirectional fashion

 

One focus of our work is engineering viral systems and labeling schemes that overcome some of the above limitations of existing techniques. Currently our lab is working on several projects using a variety of different viruses, which we design and produce in-house.