A new research method that incorporates virtual reality and brain imaging is being used to learn how the brain forms short-term memories used in decision-making.

Princeton University researchers studied rats as they negotiated a virtual maze. By following the brain activity of mice they discovered sequential patterns of neuron activity when the brain is holding a memory.

Previous research centered on the idea that populations of neurons fire together with similar patterns to each other during the memory period.

The findings illuminate what happens in the brain during “working memory,” when the mind stores information for short periods of time prior to acting on it or integrating it with other information.

Working memory is a central component of reasoning, comprehension and learning. Certain brain disorders such as schizophrenia are thought to involve deficits in working memory.

“Studies such as this one are aimed at understanding the basic principles of neural activity during working memory in the normal brain. However, the work may in the future assist researchers in understanding how activity might be altered in brain disorders that involve deficits in working memory,” said researcher David Tank, Ph.D.

In the study, the patterns of sequential neuronal firing corresponded to whether the mouse would turn left or right as it navigated a maze in search of a reward. Different patterns corresponded to different decisions made by the mice, the Princeton researchers found.

The sequential neuronal firing patterns spanned the roughly 10-second period that it took for the mouse to form a memory, store it and make a decision about which way to turn. Over this period, distinct subsets of neurons were observed to fire in sequence.

Researchers say the findings contrast with many existing models of how the brain stores memories and makes decisions.

The uniqueness of the left-turn and right-turn sequences meant that the brain imaging experiments essentially allowed the researchers to perform a simple form of “mind reading.” By imaging and examining the brain activity early in the mouse’s run down the maze, the researchers could identify the neural activity sequence being produced and could reliably predict which way the mouse was going to turn several seconds before the turn actually began.

The sequences of neural activity discovered in the new study take place in a part of the brain called the posterior parietal cortex. Previous studies in monkeys and humans indicate that the posterior parietal cortex is a part of the brain that is important for movement planning, spatial attention and decision-making.

The new study is the first to analyze it in the mouse. “We hope that by using the mouse as our model system we will be able to utilize powerful genetic approaches to understand the mechanisms of complex cognitive processes,” said co-author Christopher Harvey, Ph.D.

A unique aspect of this study was the use of virtual reality to create a maze, rather than a traditional physical maze. This approach has been under development in the Tank lab for the last several years.

The mice walked and ran on the surface of a spherical treadmill while their head remained stationary in space, which is ideal for brain imaging. Computer-generated views of virtual environments were projected onto a wide-angle screen surrounding the treadmill. Motion of the sphere produced by the mouse walking and turning was detected by optical sensors on the ball’s equator and used to change the visual display to simulate motion through a virtual environment.

To image the brain, the researchers employed an optical microscope that used infrared laser light to look deep below the surface in order to visualize a population of neurons and record their firing.

The virtual reality system, combined with the imaging system and a calcium sensor, allowed the researchers to see populations of individual neurons firing in the working brain. “It is like we are opening up a computer and looking inside at all of the signals to figure out how it works,” said Tank.

Investigators admit that studies of populations of individual neurons, termed cellular-resolution measurements, are challenging because the brain contains billions of neurons packed tightly together.

The instrumentation developed by the Tank lab is one of the few that can record the firing of groups of individual neurons in the brain when a subject is awake. Most studies of brain function in humans involve studying activity in entire regions of the brain using a tool such as magnetic resonance imaging (MRI) that average together the activity of many thousands of neurons.

“The data reveal quite clearly that at least some form of short-term memory is based on a sequence of neurons passing the information from one to the other, a sort of ‘neuronal bucket brigade,'” said Christof Koch, a neuroscientist who was not involved in the study.

The study has been published online in the journal Nature.

Source: Princeton University