Scientists Find Spatial Navigation Error-Correcting Neurons

Our brains use spatial mapping and recollection to direct us from point A to point B during daily navigation. Making a navigational error that necessitates a course correction is also commonplace. Harvard Medical School researchers have identified a specific group of neurons in a brain region involved in navigation that experience bursts of activity when mice racing through a labyrinth stray off course and repair their error.

The findings, which were published in Nature on July 19, bring scientists one step closer to understanding how navigation works while also raising new issues. These questions include what these neurons accomplish during navigation and what they do in other brain regions where they are found.

“Navigation has been studied a lot but, to our knowledge, this is the first time we’ve identified this type of error-correction signal,” said senior author Christopher Harvey, associate professor of neurobiology in the Blavatnik Institute at HMS. “I think this study adds a new direction where we can go with navigation research.”

Making a change of direction
The Harvey group has been examining the posterior parietal cortex, a region near the rear of the brain involved in spatial reasoning, as well as learning and planning motions, to better comprehend navigation. The cells that make up that region, according to the study, have mainly remained a mystery.

“There are all these different cell types in that area, but when we started this project, we didn’t know much about what these cell types might be doing,” explained lead author Jonathan Green, a research fellow in neurobiology at HMS.

Understanding how these distinct cells interact to build the neuronal circuit that controls navigation in that brain region requires elucidating their roles.

Green and Harvey went to colleague and research co-author Michael Greenberg, the HMS Nathan Marsh Pusey Professor of Neurobiology, to investigate the cell types in the posterior parietal cortex. They borrowed a technique developed in his lab that allows scientists to more precisely label cell kinds. The scientists utilized a viral capsule to introduce a gene-regulatory element into the posterior parietal cortex, causing a subtype of neurons to express a blue fluorescent protein. The researchers selectively tagged specific neurons in order to monitor their activity.

The scientists employed a technology developed in the Harvey lab that involves placing mice in a virtual reality maze: a mouse runs on a ball while a big surround screen presents a spatial navigation assignment. The aim in this scenario was to navigate a T-shaped maze to find a prize at one end. The researchers monitored brain activity in the mouse’s posterior parietal cortex as it did the test.

The researchers discovered that when a mouse made and repaired a navigational error, the subtype of neurons became activated. This was true even when they directed the mouse to err by rotating the maze or modifying the color signals. The neurons did not activate if the mouse did not make a mistake or made a mistake but did not repair it.

When the neurons became active, they did so in tandem, prompting the researchers to do a follow-up experiment in which they stimulated the cells with light. They discovered that neurons are fundamentally hardwired to each other, which means that the electrical current that tells them to fire can go directly from one cell to the next.

“These neurons were all activating together right at these moments when the mouse deviated from its route and had to correct back to get the reward, which we think means they could be really important for the learning or correction of navigational routes,” Harvey said.

A broader message?
The findings provide fascinating evidence that this subset of neurons is important in assisting the brain in correcting navigational errors, but the researchers are keen to learn more about how and why.

Harvey is curious whether this error-correction signal helps the brain learn navigational routes, which he refers to as “a missing piece of the puzzle for how navigation happens.” To investigate this theory, the researchers are doing tests in which they disrupt the firing of neurons and observe how this affects the mouse’s navigational skills.

“We want to find out if this signal is involved in driving corrections on a moment-to-moment basis, or if it is acting on a longer time scale by helping the circuit learn the correct actions over time,” Green said.

Although the study was done in mice, Green noted that humans have an analogous cell type, so “this error-correction signal that we see in mice could actually be quite relevant to what is happening in our brain.” However, more research is needed to confirm whether this is the case.

This subtype of neuron is also found in other brain regions that are highly engaged in navigation, such as the visual cortex and the hippocampus, which is the epicenter of learning and memory. Green wants to look at what neurons are doing in these other areas to see if they play a larger part in error correction and learning.

The researchers also intend to apply their experimental approach to other subsets of neurons in the posterior parietal cortex, many of which are also found in other brain areas, with the hope of uncovering new cell types with specific functions.

“If we can understand what all these subsets of neurons are doing in different brain areas, the hope is that we can get at some generalized functions for the cells that move us closer to understanding how this neural circuit, which is replicated across brain areas, works,” Green said.

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