Viviana Gradinaru (BS '05) might one day be getting inside your head—but in a good way. An assistant professor of biology at Caltech, Gradinaru is trying to map out the brain's wiring diagrams. Gradinaru will discuss her work at 8:00 p.m. on Wednesday, December 5, in Caltech's Beckman Auditorium. Admission is free.
Q: What do you do?
A: I'm a neuroscientist. I'm trying to understand the brain by turning nerve cells in specific circuits on or off and seeing what the effects are. This is very difficult with conventional methods, one of which is to put in an electrode and pass a current that stimulates all the cells in the vicinity in a nondiscriminate fashion.
What we do instead is introduce modulators into well-defined sets of cells. These modulators are light-sensitive proteins called opsins, similar to the rhodopsin that's part of the visual system in your eye. Opsins form channels in the cell wall, and when they absorb light, they change shape and allow ions to flow into or out of the cell. So by using different opsins, we can either inhibit or excite neurons in a reversible fashion. Neurons are not naturally responsive to light, so when we light up the brain through a fiber-optic thread, we know exactly what cells we are affecting. We use genetic engineering to introduce our optical switches into different cell types. It's almost like giving ZIP codes to the opsins to tell them exactly where to go.
Q: How did you get into this line of work?
A: When I was an undergraduate here at Caltech, I did a very extensive research project in the lab of professor Paul Patterson. That was where I fell in love with neuroscience. It started as a SURF [Summer Undergraduate Research Fellowship] project, and I ended up staying in his lab until I graduated.
It so happens that I was working on a motor-disorder project—on Huntington's disorder—trying to understand what causes the disease. I was working on protein aggregation in cultured cells, because protein aggregation was a known phenomenon in degenerated nerve-cells in Huntington's disorder. However, I could see how remote it was from the real thing. Working in a dish. And I felt, "we should be doing this in the real thing." But the tools were not available.
When I moved to Stanford for my PhD work, there was this new lab just starting. Professor Deisseroth started the same year I did, and his lab developed this technology and also coined the name optogenetics for it. I wanted to look at the circuits involved in motor behavior, so I joined his lab to work on Parkinson's disorder. However, the technology was rather early, and I ended up spending a lot of time perfecting it before I could probe the circuits. But it was well worth it: I learned the value of making your own tools.
Q: What does this tell us that we can apply to people?
A: We can find out more about the circuitry underlying a defined disease, and by understanding the circuitry, we have a better chance to tackle the disease itself. Parkinson's is an interesting example. A very good therapy for Parkinson's after drug therapy stops working is to implant electrodes in the motor centers of the brain. Zapping those brain cells at 100 Hertz—a very high frequency—takes care of the tremor and lets people walk again, which is rather miraculous. It works very well, but we don't understand why it works, because electrical stimulation is nonspecific. We don't know what circuits are being affected. Optogenetics can help here, as a tool to generate information about both the healthy brain and the diseased brain.
