In brief:
How the brain tracks distance: MPFI scientists identified how hippocampal neurons encode distance traveled without relying on visual cues.
A new neural code: Neuronal activity patterns act as a two-phase code to mark movement onset and track elapsed distance.
Why it matters: These patterns may help the brain stitch moment-to-moment experiences into a memory of an event.
Alzheimer's relevance: The work may offer insight into early navigation problems commonly seen in Alzheimer's disease.
Whether you are heading to bed or seeking a midnight snack, you don't need to turn on the lights to know where you are as you walk through your house at night. This hidden skill comes from a remarkable ability called path integration: your brain constantly tallies your steps and turns, allowing you to mentally track your position like a personal GPS. You're building a map by tracking movement, not sight.
Scientists at the Max Planck Florida Institute for Neuroscience (MPFI) think that understanding how the brain performs path integration could be a critical step toward understanding how our brain turns momentary experiences into memories of events that unfold over time. Publishing their findings this week in Nature Communications, they have made big strides toward this goal. Their insights may also provide information about what may be happening to patients in the early stages of Alzheimer's disease, whose first symptoms are often related to difficulty tracking distance or time.
Navigating without landmarks
In their study, the team trained mice to run a specific distance in a gray virtual reality environment without visual landmarks, in exchange for a reward. The animals could only judge how far they had traveled by monitoring their own movement, not by relying on environmental cues. As mice performed this task, the scientists recorded tiny electrical pulses that neurons use to communicate, allowing them to observe the activity of thousands of neurons. They focused on the activity of neurons in the hippocampus, a region essential for both navigation and memory. Using computer modeling, they then analyzed these signals to reveal the computational rules the brain uses for path integration.
"The hippocampus is known to help animals find their way through the environment. In this brain region, some neurons become active at specific places. However, in environments full of sights, sounds, and smells, it is difficult to tell whether these neurons are responding to those sensory cues or to the animal's position itself," explains senior author and MPFI group leader Yingxue Wang. "In this study, we removed as many sensory cues as possible to mimic situations such as moving in the dark. In these simplified conditions, we found that only a small number of hippocampal cells signaled a specific place or a specific time. This observation made us wonder what the rest of the neurons were doing, and whether they were helping the animal keep track of where it is by integrating how far and how long it had been moving, a process called path integration."
A neural code for path integration
The scientists discovered that during navigation without landmarks, most hippocampal neurons followed one of two opposite patterns of activity. These patterns were crucial for helping the animals keep track of how far they had traveled.
In one group of neurons, activity sharply increased when the animal started moving, as if marking the start of the distance-counting process. The activity of these neurons then gradually ramped down at different rates as the animal moved further, until reaching the set distance for a reward. A second group of neurons showed the opposite pattern. Their activity dropped when the animal started moving, but gradually ramped up as the animal traveled farther.
The team discovered that these activity patterns act as a neural code for distance, with two distinct phases. The first phase (the rapid change in neural activity) marks the start of movement and the beginning of distance counting. The second phase (the gradual ramping changes in neural activity) counts the distance traveled. Both short and long distances could be tracked in the brain by using neurons with different ramping speeds.
"We have discovered that the brain encodes the elapsed distance or time needed to solve this task using neurons that show ramping activity patterns," said lead scientist Raphael Heldman. "This is the first time distance has been shown to be encoded in a way that differs from the well-known place-based coding in the hippocampus. These findings expand our understanding that the hippocampus is using multiple strategies - ramping patterns in addition to the place-based coding - to encode elapsed time and distance."
When the researchers disrupted these patterns by manipulating the circuits that produce them, the animals had difficulty performing the task accurately and often searched for the reward in the wrong location.
Future impact
Dr. Wang notes that "understanding how time and distance are encoded in the brain during path integration is especially important because this ability is one of the earliest to degrade in Alzheimer's disease. Patients report early symptoms of getting spatially disoriented in familiar surroundings or not knowing how they got to a particular place."
The research team is now turning its efforts to understand how these patterns are generated in the brain, which may help reveal how our moment-to-moment experiences are encoded into memories and how they might be disrupted in the earliest stages of Alzheimer's disease.
This work was funded by the Max Planck Society, the Max Planck Foundation, and the National Institutes of Health. This content is solely the authors' responsibility and does not necessarily represent the official views of the funders.
