Testing the hypothesis

Moore has been thinking about the role of blood in the brain for a long time. But, he says, "I didn't even want to talk about it until I could test it." As a grad student working in others' labs, he was committed to research already under way. And even once he got his own lab, launching the project was no simple matter. "Frankly," he says, "the main thing that held me back was, I couldn't come up with an answer to the question 'How do you independently manipulate the blood flow?'" Working with a dish of cells wasn't an option; he had to do his experiments in living, thinking animals.

The neural dynamics of complex human behaviors such as conducting a conversation or hitting a fastball are governed by cell-level processes like those revealed by the finger tap experiment. But complex behaviors emerge from activity in many different parts of the brain, which makes them more difficult to study in the lab. And even during a simple experiment like the finger tap, you can't open up a healthy person's brain and probe individual neurons. So Moore does most of his studies in rats--"model systems where we can actually do the down-and-dirty details," he says.

Moore has done some preliminary tests of the hemo-neural hypothesis by applying a drug called pinacidil, which increases blood flow, to rats' brains; he presented the results at a conference a few years ago. But this approach is sloppy. It's very difficult to limit the application of pinacidil, a chemical like the one found in Rogaine, to a small group of blood vessels and cells. Moore knew that the behavior of single cells determines neural dynamics, and he needed a way to control blood flow at a much finer level.

This spring, Moore and the Media Lab's Boyden began working out a way to regulate blood flow in very small regions of the brain. Through a feat of genetic engineering, Boyden had already developed a method for altering neurons in living animals so that they can be electrically activated and deactivated by blue and yellow laser light. He uses a virus to insert into neurons a gene that codes for an altered version of a protein from light-activated cells in the retina (see "The TR35," September/October 2006).

In collaboration with Moore, Boyden has developed a way to apply the technique he used in neurons to the smooth-muscle cells that surround blood vessels in rats' brains. Once the muscle cells are modified, the vessels should dilate and contract in response to light, letting more or less blood through. "For the experimental question, it's a fantastic invention," Moore says of Boyden's work. "Now instead of the brain controlling it, I hope to control local blood flow with a laser."