Li Zhang, assistant professor of physiology and biophysics at the Keck School of Medicine of USC and a member of the Zilkha Neurogenetic Institute, has been named to the Searle Scholars Program, one of the most prestigious awards available to young faculty working in the life sciences.

Zhang is the first Searle Scholar to be chosen from the Keck School of Medicine, and was one of only 15 selected from a pool nominated by more than 100 major research institutions across the United States. These scientists’ disciplines range from chemistry and bioengineering to genomics and computation.

The award carries with it $240,000 in funding, given out over three years.

“We are very pleased that the Searle Scholars program recognized the importance of Li’s research with this prestigious award,” said Keck School Dean Brian E. Henderson. “The goal of our naming gift from the W.M. Keck Foundation was to increase our ability to attract and recruit first-rate scientists into modern research buildings like the Zilkha. This award shows us that our plan to recruit excellent faculty is reaping immediate benefits that will add to the Keck School’s growing stature.”

Zhang joined the Keck School faculty in August 2004 after receiving his doctorate from UC San Diego and finishing postdoctoral work at UC San Francisco.

“The Searle Scholarship gives me a great opportunity,” said Zhang. “Every year, the program holds an annual meeting where you get to talk with all the former Searle Scholars, many of whom have gone on to do important work in various fields. It will be wonderful to interact with these brilliant people and exchange research ideas.”

Zhang’s work focuses on the development and function of the brain’s cerebral cortex, the part responsible for perception, reasoning, learning and memory. “I’m trying to determine the neural basis for cortical function and development,” he explained.

As mammals—including humans—grow from infancy to adulthood, the perceptual component of their brain continues to mature, Zhang said. “But how that maturation is controlled is virtually unknown.”

More specifically, Zhang is trying to understand the microstructure of the brain’s cortex—the way one neuron connects with other neurons down an increasingly complex line. “There are hundreds of billions of neurons in the human brain,” he noted. “And each one of them may make connections with thousands of other neurons.”

To try to get a handle on this seemingly incomprehensible complexity, Zhang is zeroing in on one part of the sensory cortex in rodents: the auditory cortex. “We chose this because rodents have advanced hearing comparable to higher mammals,” he said.

Using techniques from electrophysiology, imaging and molecular biology, he will try to break down the circuitry by examining the signals received by single neurons. Using a technique called in-vivo whole-cell recording, Zhang said, “we can dissect inputs into two categories: excitatory or inhibitory. We can predict from their interaction what the basic property of the neuron’s output will be.”

Additionally, he will use multiphoton laser scanning microscopy, an advanced imaging technique, to penetrate fairly deep into a living cortex—a few hundred microns below the surface—and visualize single cells in action. Pairing that information with the information derived from the whole-cell recordings and from various biochemical assays, Zhang said, he should be able to come up with a more accurate picture of how neurons in the cortex connect.

Zhang said he hopes he also will be able to use this information to understand the developmental rules that determine how the circuitry of the cortex develops over time as the animal matures. “I hope to pin down the critical factors of the neural circuitry for the functional development of the sensory cortex,” he said.

Ultimately, Zhang said, this understanding of normal brain function and structure will allow for better insight into the neural basis for developmental and aging-related neurological diseases such as Alzheimer’s disease.

Since 1980, the Searle Scholars Program has been awarding grants to academic institutions to “support the independent research of outstanding individuals who are in the first or second year of their first appointment at the assistant professor level, and whose current appointment is a tenure-track position,” according to the program’s Web site.

Over the last 25 years, the Searle Scholar program has funded 348 researchers from the United States, Australia, The Netherlands, and the United Kingdom.