Tosches Lab and Collaborators Establish New Genetic Tools for Neuroscience Research in Amphibians

Expanding scientific knowledge hinges on the development and application of new research tools. To study the nervous system, genetic tools for the precise visualization and manipulation of neurons are critical. However, such tools are available just for a handful of species, like mice and fruit flies. A new study from the Tosches lab at Columbia University and the Sweeney lab at the Institute of Science and Technology Austria has established the use adeno associate viral vectors (AAVs) in amphibians, opening the door to new research into brain structure and function, as well as development and evolution.

AAV vectors are genetically-engineered particles with a protein “coat”, called the capsid, and a genetic “cargo”, which is the transgene delivered to cells. With their long-term expression and limited cytotoxicity, AAVs have proven particularly efficient at introducing genetic material to the mammalian nervous system. Until now, however, AAVs have been difficult to implement in amphibians—organisms which have been integral to research into central nervous system development, regeneration, function, and evolution. Failure to apply AAVs in amphibians has left research in organisms like frogs and salamanders relying on less efficient and more time-consuming methods of genetic manipulation. 

In the new paper published in Developmental Cell, the authors screen AAVs with different capsids to compare the transduction of neurons in three different and distantly related amphibian species, both before and after the animals undergo metamorphosis. They go on to show that AAVs can be used to identify groups of neurons undergoing development at the same time (known as isochronic cohorts), as well as to target adult neurons and discover their projections in the brain. These new applications provide access to amphibian neural circuitry with temporal and spatial specificity. In addition to establishing the use of AAVs in amphibians, the paper serves, more generally, as a protocol for implementing AAV tools in new vertebrate species.

Eliza Jaeger, a graduate student in the Tosches lab and co-first author on the publication is excited to see how this tool can impact the field. “With AAVs in our amphibian neuroscience toolkit, we can now delve into new ways of understanding the functions of different neuron types,” Jaeger says.

The collaborative study was funded by an NSF EDGE grant and involved several labs around the world, including Dr. Darcy Kelley, also in the Department of Biological Sciences, who was instrumental in bringing this group of researchers together, securing the EDGE funding, and has been a vocal advocate for studying amphibian neuroscience.