PITTSBURGH -- Carnegie Mellon University neuroscientist Nathan Urban has received a $979,000 grant as part of a joint National Institute of Mental Health (NIMH) and National Science Foundation (NSF) program to elucidate how cellular and molecular changes in neurons lead to their synchronized firing. Ultimately, this work is critical to understanding brain disorders, such as schizophrenia, which are thought to involve disruption of neuronal synchronization. The research is part of a project Urban is conducting in collaboration with Bard Ermentrout, University Professor of Computational Biology in the University of Pittsburgh Department of Mathematics.
Neuronal synchronization, especially of high-frequency oscillations called gamma oscillations, is thought to be involved in perception and consciousness. Alterations in this synchrony have been implicated in schizophrenia, a chronic, severe and disabling brain disorder that affects about one percent of people worldwide, according to the NIMH.
"Understanding how normal gamma oscillations are generated is important for understanding disorders such as schizophrenia, which are associated with altered gamma activity," said Urban, an assistant professor of biological sciences in the Mellon College of Science.
The acute symptoms of schizophrenia are currently managed with pharmaceuticals, but understanding the basic mechanisms that underlie neuronal synchronization -- and how it goes awry -- may allow clinicians to treat the root cause of this disorder and not just the symptoms, Urban added.
Urban's NIMH/NSF funding arises from his discovery of stochastic synchrony, a novel mechanism for generating synchronous neuronal firing. With this latest award, he will further investigate the cellular- and circuit-level properties that orchestrate this coordinated neuronal activity.
"Using a combination of experimental and computational techniques, we have described stochastic synchrony, a mechanism by which neurons are synchronized by random, 'noisy' inputs," Urban said. "We are now investigating which properties of neurons are most critical for the development of this 'noise'-induced synchronization."
Neurons convey messages more effectively when they fire together, and networks of neurons often fire together because they are directly connected. However, groups of neurons also fire in chorus even when they are not directly connected. Until now, this type of synchrony has remained difficult to understand. But stochastic, noise-induced synchrony demonstrates how coordinated firing can be caused by a variety of different kinds of random inputs.
Bursts of synchronized neural electrical activity, whether connectivity- or noise-induced, occur at different rates. For example, during sleep the brain's neurons send electrical signals at around four times a second. Higher-level cognitive activities are thought to result from synchronized neuronal firing at about 40 times a second, or what is called the gamma frequency.
Urban has already shown experimentally that noisy inputs can generate oscillatory synchrony in specific types of neurons in the mouse olfactory bulb, the area of the brain responsible for distinguishing odors. Noisy inputs in the olfactory bulb may account for the recognized development of synchronous oscillations in the gamma frequency range, noted Urban, who is exploring this phenomenon further.
"By exploring how gamma oscillations naturally arise in this system, we hope to better understand how altering cellular and circuit-level properties can interfere with the development of normal gamma oscillations," Urban said. He also noted that working out these basic mechanisms in this system could one day help clinicians detect the earliest development of schizophrenia and develop more targeted interventions.
Urban and Ermentrout are focusing on the mouse's olfactory bulb, which they call an elegant system in which to explore the relationship between circuit properties and synchronous oscillations. A mouse can recognize and process tens of thousands of odors, many of which are critical to its survival, including the scent of food and prey. Single molecules of odors can activate widely distributed regions of the olfactory bulb, regions that work together in synchrony to represent an odor. These networks of olfactory bulb neurons can be studied directly by recording activities of just one or two cells at one time. Understanding how the intrinsic properties of neurons and the local circuitry of the olfactory bulb generate synchrony is applicable to all brain networks, according to the researchers.
The Mellon College of Science at Carnegie Mellon conducts innovative research and educational programs in biological sciences, chemistry, physics, mathematics and several interdisciplinary areas. For more information, visit www.cmu.edu/mcs.