Will talk about: Rabies-based tools for elucidating neural circuits and linking connectivity to function
Edward Callaway heads the Organization and Function of Cortical Circuits group at the Systems Biology Laboratories of the Salk Institute for Biological Studies in La Jolla, CA, USA. He is Professor and senior fellow at the Crick-Jacobs Center for Theoretical and Computational Biology of the Salk Institute and also adjunct Professor of the Department of Neuroscience at the University of California at San Diego.
Dr. Callaway holds a Bachelor of Science degree in biology from Stanford University, Stanford, CA, USA, and a PhD in neurobiology from California Institute of Technology, Pasadena, CA, USA. He worked with Lawrence Katz as a postdoc 1988-92 at The Rockefeller University, New York, NY, USA, and at Duke University, Durham, NC, USA before becoming an Assistant Professor at the Department of Physiology and Neuroscience at the University of Colorado School of Medicine, Denver, Co, USA. He joined the Salk Institute in 1995 and was appointed Professor there in 1996.
Dr. Callaway won the McKnight Endowment Fund for Neuroscience, Technological Innovations Award in 2006 for “Using Viral Vectors to Probe Sensory-Motor Circuits in Behaving Non-human Primates” and was elected Associate of the Neurosciences Research Program in 2009.
To understand the mechanisms by which neural circuits process information, it is necessary to resolve connectivity with high resolution, to correlate connectivity with function, and to manipulate the activity of defined circuit components. Recent advances in the development of molecular, genetic and viral based tools are now making this possible at the level of resolution of specific cell types and even single neurons. I will describe recent progress in my lab, developing and using rabies virus-based systems for tracing neural circuits and linking them to function. Because rabies virus spreads transsynaptically, exclusively in the retrograde direction, and only between connected neurons, it is a very powerful tool for studies of neural circuits. Our new tracing systems are based on rabies viruses whose glycoprotein gene has been deleted, making it possible to both control the transsynaptic spread of the virus and to also select specific neurons or neuron types for primary infection. These viruses also express transgenes, such as fluorescent proteins, at very high levels allowing clear visualization of detailed neuronal morphology. Building on these viruses we have developed protocols and reagents that make it possible to label neurons in vivo that are directly presynaptic to a single targeted neuron or to label the direct inputs to a population of neurons of genetically-defined type from a targeted brain region. Because the rabies virus leaves cells viable for weeks, it is possible to combine rabies labelling of connectionally-defined neuronal populations with studies monitoring or manipulating their activity. This is facilitated by the production of rabies viruses that express transgenes such as genetically expressed activity indicators or channelrhodopsins. Rabies viruses expressing genes for the control of gene expression, such as Cre-recombinase or the Tet transactivator, allow rabies labelling of defined circuits to interface with mouse lines that express transgenes of interest under the control of these proteins.
This work was supported by NIH, HFSP, and the Gatsby Foundation.