Newswise — Complex biochemical signals that coordinate fast and slow changes in neuronal networks keep the brain in balance during learning, according to an international team of scientists from the RIKEN Brain Science Institute in Japan, UC San Francisco (UCSF), and Columbia University in New York.

The work, reported on October 22 in the journal Neuron, culminates a six-year quest by a collaborative team from the three institutions to solve a decades-old question and opens the door to a more general understanding of how the brain learns and consolidates new experiences on dramatically different timescales.

Neuronal networks form a learning machine that allows the brain to extract and store new information from its surroundings via the senses. Researchers have long puzzled over how the brain achieves sensitivity and stability to unexpected new experiences during learning - two seemingly contradictory requirements.

A new model devised by this team of mathematicians and brain scientists shows how the brain's network can learn new information while maintaining stability.

To address the problem, the team turned to a classic experimental system. After birth, the visual area of the brain's cortex undergoes rapid modification to match the properties of neurons when seeing the world through the left and right eyes, a phenomenon termed "ocular dominance plasticity," or ODP. The discovery of this dramatic plasticity was recognized by the 1981 Nobel Prize in Physiology or Medicine awarded to David H. Hubel and Torsten N. Wiesel.

ODP learning contains a paradox that puzzled researchers--it relies on fast-acting changes in activity called "Hebbian plasticity" in which neural connections strengthen or weaken almost instantly depending on their frequency of use. However, acting alone, this process could lead to unstable activity levels.

In 2008, the UCSF team of Megumi Kaneko and Michael P. Stryker found that a second process, termed "homeostatic plasticity," also controls ODP by tuning the activity of the whole neural network up in a slower manner, resembling the system for controlling the overall brightness of a TV screen without changing its images.

By modeling Hebbian and homeostatic plasticity together, mathematicians Taro Toyoizumi and Ken Miller of Columbia saw a possible resolution to the paradox of brain stability during learning. Dr. Toyoizumi, who is now at the RIKEN Brain Science Institute in Japan, explains, "We were running simulations of ODP using a conventional model. When we failed to reconcile Kaneko and Stryker's data to the model, we had to develop a new theoretical solution."

"It seemed important to explore the interactions between these two different types of plasticity to understand the computations performed by neurons in the visual area," Dr. Stryker adds. Testing the new mathematical model in an animal during experimental ODP was necessary, so the teams decided to collaborate.

The theory and experimental findings showed that fast Hebbian and slow homeostatic plasticity work together during learning, but only after each has independently assured stability on its own timescale. "The essential idea is that the fast and slow processes control separate biochemical factors," said Dr. Miller, of Columbia University’s Mortimer B. Zuckerman Mind Brain Behavior Institute.

"Our model solves the ODP paradox and may explain in general terms how learning occurs in other areas of the brain," said Dr. Toyoizumi. "Building on our general mathematical model for learning could reveal insights into new principles of brain capacities and diseases."

Reference:Taro Toyoizumi, Megumi Kaneko, Michael P. Stryker, and Kenneth D. Miller, Modeling the dynamic interaction of Hebbian and homeostatic plasticity. Neuron, doi:10.1016/j.neuron.2014.09.036.

About The Mortimer B. Zuckerman Mind Brain Behavior InstituteColumbia University’s Mortimer B. Zuckerman Mind Brain Behavior Institute is an interdisciplinary hub for scholars across the university, created on a scope and scale to explore the human brain and behavior at levels of inquiry from cells to society. The institute’s leadership, which includes two Nobel Prize-winning neuroscientists, and many of its principal investigators will be based at the 450,000-square-foot Jerome L. Greene Science Center, now rising on the university’s new Manhattanville campus. In combining Columbia’s preeminence in neuroscience with its strengths in the biological and physical sciences, social sciences, arts, and humanities, the institute provides a common intellectual forum for research communities from Columbia University Medical Center, the Faculty of Arts and Sciences, the School of Engineering and Applied Science, and professional schools on both the Morningside Heights and Washington Heights campuses. Their collective mission is to further our understanding of the human condition and to find cures for disease.

About UCSFUCSF is the nation’s leading university exclusively focused on health. Now celebrating the 150th anniversary of its founding as a medical college, UCSF is dedicated to transforming health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with world-renowned programs in the biological sciences; a preeminent biomedical research enterprise; and top-tier hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospitals.

About the RIKEN Brain Science InstituteThe RIKEN Brain Science Institute (BSI) performs cutting-edge neuroscience research in the service of society and has earned an international reputation as an innovative center for research and training. Researchers at BSI seek to understand brain functions from molecules to neural circuits to cognition, using methods drawn from a wide range of disciplines. BSI is also leading efforts to provide career development for researchers in Japan and around the world. Website: