Ed Callaway on Mapping Brain Connectivity, Mentorship, and the Dream Experiment

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About ten years ago a group of neuroscientists led by Professor Ed Callaway realized they would soon be able to label all the presynaptic inputs to an individual neuron by using a modified rabies virus. The ability to map neural circuits and the direct synaptic inputs to individual neurons was unprecedented at the time and held the potential to transform our understanding of how neural circuits in the brain are organized. In a podcast, Ed (a systems neuroscientist who also happened to be my PhD advisor back in the day) and I met up in San Diego, CA, to talk about how he and Ian Wickersham developed the use of rabies virus to label neurons that form direct connections to a particular cell type. It’s a story of hard work across scientific disciplines, focus, perseverance and serendipity.

Since then, progress in the lab has mirrored the revolution taking place in the field of neural circuits. Fueled by cutting-edge methods for labeling neural circuits of specific cell types, imaging their activity, and testing how subsets of neuronal populations affect others, the field and the Callaway lab have catapulted forward with more integrated experiments looking at cell types, circuits, activity, and causality. Also, for the past few years his lab has been doing behavior experiments. It’s clear that things only continue to get more interesting as his lab employs any and all methods that make sense to try, or that are even crazy to try! As he said, he’s tried a lot of things in his lab over the years that didn’t work, and it was because of the failures he and his lab made it to so many successes.

When I asked Ed about his dream experiment, he immediately had one in mind that utilizes all the latest in neuroscience technologies plus methods that have yet to be invented. Now, as I imagine neuroscientists working to unravel the mysteries of the brain, achieving remarkable feats toward a massive amount of data about neural connectivity and integration of synaptic inputs during behavior and cognition, I see the field marching toward the reaches of Ed Callaway’s imagination.

Since he started graduate school at California Institute of Technology, Ed has been on the forefront of science, and has been influenced by some remarkable scientists along his career path. In our conversation, Ed talks about his mentors, David Van Essen and Larry Katz, and the impact they had on his own science when he started out studying developmental biology (Check out the podcast to find out why Ed says the field needs a revival in developmental biology). He describes the focus and courage necessary to do the kinds of groundbreaking and challenging experiments he’s done. In the podcast, we get to know Ed as a scientist and a person, showcasing his thoughtfulness and graciousness.

If you’re a neuroscientist interested in mapping neural connections, then you probably want to get your hands on viral circuit tracing methods, if you haven’t already. The Salk Institute for Biological Studies has a core facility where you can get G-deleted rabies viruses, and there are hundreds of modified rabies viruses on Addgene specifically for the use of labeling synaptic connections. Ed’s lab currently has funding to test the array of modified rabies viruses and reagents to fully characterize them for use in labeling synaptic connections, a great gift to the scientific community.

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