As a child in Rome, Massimo Scanziani grew up on a steady diet of culture. Discussions at the family dinner table revolved around history, literature, and art—not neuroscience.
But a deep interest in nature led him to study science and the mysteries of the brain. Although his career path diverged from the marvels of Roman antiquities and the nuances of Renaissance frescoes, Scanziani wants to understand how we think about such things. In short, he wants to eavesdrop on the brain as we take in a masterpiece or are moved by it.
A biology professor and neurophysiologist at the University of California, San Diego, Scanziani is unraveling the circuitry of the cortex, the part of the brain that processes thought, emotion, perceptions—all the things that come into play when we view art, listen to a concerto, or think about an event in history. With the help of animal models, he and a host of colleagues are building a working picture of the circuits in the cortex that control our thoughts, actions, and perceptions. He focuses on the wiring of the cortex, the largest part of the brain and the area most closely associated with higher brain functions such as reasoning, speech, emotions, and memory, among others. "The mystique of the brain is in the cortex," Scanziani explains. "I want to understand how thought and sensation are organized in time and space."
Scanziani designs artful experiments to probe the principles that guide brain function. "Precision in a question contains the way to get the answer, and a clear answer is something very beautiful," he says, explaining that a good experiment can both explain nature and open up new questions. He teaches his students that even failed experiments can be valuable. "Failures force you to think about the experiment again and the questions you are asking," he says.
Scanziani's team of researchers is focused on explaining how neurons connect in just milliseconds to create a circuit that lets us process information in a picture, register an odor, or think. His group studies specific neurons, called interneurons, that play the role of traffic cops in the congested streets of the cortex, directing neuronal impulses to make sure messages flow smoothly. "You need neurons that inhibit activity in the brain and neurons that promote activity. You need green and red signals."
Scientists have found that interneurons often communicate with other neurons in classic patterns. These can be thought of as parts of simple circuits linking excitatory (green light) and inhibitory (red light) neurons. Scanziani's lab has shown that these circuits work the same way in different parts of the brain, indicating that they are basic modules of how the cortex is organized.
To examine these simple circuits, Scanziani and his lab record the electrical activity of individual neurons in slices of rodent brains, which can be kept alive for short periods under a microscope. They have found that excitatory and inhibitory neurons work together to send specific messages in the right direction. One experiment, demonstrating that a single inhibitory neuron can dramatically alter complete circuits, has been described as the kind of discovery that rattles entire fields of research.
Scanziani's work has also shown that nerve cells in general perform highly specialized jobs. To make sense of the barrage of incoming information that confronts the brain, neurons must pay attention not only to the arrival of signals but also to where they come from, how frequently they arrive, and what intensity they have. Scanziani has shown that different neurons are particularly tuned in to certain characteristics of incoming information. Some simply note that information has arrived in the form of an electrical stimulus, for example, while others are more sensitive to the frequency of a signal. "It is clear to everybody that there are many different kinds [of neurons], but we don't yet know their specific roles in organizing information in the brain," he says.
As an HHMI investigator, Scanziani wants to extend his experiments on rodent brains from the petri dish to live animals. His lab is developing tools that will allow them to manipulate the circuits—activating, silencing, or completely eliminating them—in animal models. "We think the basic behaviors of the circuits can be repeated in the intact animal," he says. "Maybe in a year or two we'll get to that level."
No matter what the experiment, Scanziani will be waiting anxiously for the answer. "I always want to know immediately the outcome of an experiment. I'm dying to know how it turned out."