Researchers propose model of neural circuit underlying working memory

Novel computational neuroscience model offers new areas for experimentation

Our ability to understand speech or decide which fruit in the store is freshest depends on the brain’s dexterity in integrating information over time. The prefrontal cortex, where working memory resides, plays a critical role in helping us make these countless everyday decisions. A novel computational study by Brandeis researchers in this week’s issue of the Proceedings of the National Academy of Sciences proposes for the first time a neuronal model for the mechanisms underlying a time-related task in this complex decision-making process.

Essentially, the study shows that neurons in the prefrontal cortex fire with greater or lesser intensity to finely control, or inhibit behavior, based on a neuronal feedback signal, or circuit mechanism. Such integral feedback control is probably at work in many regulatory areas of the body, such as temperature control and feelings of satiety to prevent overeating, but this is the first time this mechanism has been suggested as a role of neuronal firing.

The findings provide a framework for understanding how neurons operate in a part of the brain that controls behavior and which is often compromised in people with mental health problems such as schizophrenia, a disease that can entail problems with short-term memory tasks and misperceptions about the immediate environment.

“This novel study gives us another computational tool with which to explore the incredibly complex mechanisms at work in working memory – an important portal to understanding many aspects of mental health and disease,” said Miller.

Paul Miller, who authored the paper along with Xiao-Jing Wang, compared the neuronal integral feedback control mechanism, a concept common in engineering, to the way a home boiler works.

“When the boiler is on, the temperature of the room rises, increasing the rate of heat production from the boiler. Once the temperature of the room is sufficiently high, the thermostat switches off the boiler. This is feedback inhibition – a sufficiently high temperature switches off the boiler, the same way in our neuronal circuit that sufficiently high neuronal activity will switch off earlier firing neurons,” explained Miller.

“While a perfectly insulated room would maintain the high temperature, most rooms have leaks, so over time, would cool down. An important area of investigation in neuroscience is how neurons can make their leak timescales long enough to be useful for working memory tasks,” added Miller.