UCLA researchers created a virtual world to determine how individual neurons track both where we are and where we move. Understanding how these cells function is key to understanding how the brain makes and retains memories, which are vulnerable to such disorders as Alzheimer’s and PTSD. They published their findings on May 2 in the online edition of the journal Science.
“Ultimately, understanding how these intricate neuronal networks function is a key to developing therapies to prevent such disorders,” explained senior author Mayank Mehta, who holds joint appointments as a professor in the UCLA departments of neurology, physics, and astronomy. For decades, scientists have pondered how neurons make maps of space. Several different types of stimuli are known to influence neuronal maps: for example, visual cues of the surrounding physical environment, other sensory cues like smell, and the body’s innate knowledge of how fast it moves through space. However, the mechanisms by which groups of neurons combine these different inputs to make these precise mental maps are unknown. To solve this puzzle, neurophysicists at UCLA built an immersive virtual reality to manipulate these cues, then measured the activity of individual neurons in rats.
What they found was surprising: while neurons in the real world fire at an absolute, fixed position, in the virtual world, deprived of certain sensory cues, the cells switched to a different strategy, computing the relative positions of the animal; that is, the distance the animal traveled in this virtual world. Other cells shut down completely, suggesting that different sensory cues strongly influence these neurons. The investigators also discovered that in this virtual world, the brain’s theta rhythm, the rhythmic firing of neurons that normally speed up or slow down depending on how fast an animal is moving, were profoundly alerted, instead maintaining one steady, rhythmic pattern.
Individual neurons located in the brain’s hippocampus create maps of space; thus, they are termed place cells. These cells are crucial for learning and memory, and are involved in such disorders as Alzheimer’s disease and PTSD when they are damaged. It is known that place cells respond to a variety of sensory cues, visual cues of the surrounding physical environment, called distal cues, self-motion cues, the body’s innate knowledge of how fast it travels through space (gait), and other sensory cues, such as smells, sounds and textures. Dr. Mayank Mehta asks if they are the same maps created by different sensory methods? Do these maps cooperate with each other, or do they compete?
For about 40 years, researchers have felt that our neuronal maps of space are based on the landmarks surrounding the subject such as a tall tree or a building. However, in the real world, Dr. Mehta explains, other cues are also present, such as the smell of the local pizzeria, the sound of a nearby subway tunnel, the tactile feel of your feet on a surface. These other sensory cues, what Dr. Mehta likes to call “stuff,” were thought to have a small influence on place cells. But no one really knew for sure. In the real world it is impossible to get rid of all this other sensory stuff. Thus, the precise influence of distal cues and gait in generating neuronal maps of space was unknown. To get around this, Mehta and his colleagues built a virtual reality maze. Rats, held by a harness, walked or ran on a ball that would rotate whenever they moved. The running movement of the ball generated a movement of distal cues that were projected on screens that surrounded them. It gave the rats the illusion they were running in the real world based on these cues; however, it was the world that was running by them. All the other non-specific “stuff,” such as odors, was eliminated in the virtual world; only the distal cues and the self-motion cues were present. The researchers then used micro-electrodes ten times thinner than human hair to measure the activity of some 3,000 neurons in the brains of six rats. The rats ran on a simple maze, just as you would walk from your door to your parked car and back. They did the same simple task in the real world and in virtual reality; the only difference between the two worlds was that all the non-specific sensory stuff was eliminated in the virtual world.
Using this virtual reality the UCLA team discovered that eliminating other sensory cues had a tremendous effect on the activity of these cells: fully half of the neurons being recorded became inactive in the virtual world, even though the distal cues and gait were similar in both the virtual and real worlds. This revealed that this other sensory stuff, once thought to play a minor role in activating the brain, actually has a major influence on place cells.
In the real world the active place cells represent absolute position, spiking at the same place irrespective of movement direction, which is consistent with older experiments, said Dr. Mehta. For example, if a neuron spiked five feet away from the front door on the way to the car, the neuron will again fire five feet away from the door while walking back from the car. “But, in the virtual world,” he said, “we found that the neurons almost never did that. Instead, the neurons spiked at the same relative distance in the two directions as the rat moved back and forth. In other words, going back to the front door to car analogy, in a virtual world the cell that fires five steps away from the door when leaving your home would not fire five steps away from the door upon return. Instead, it would fire five steps away from the car when leaving the car. Thus, these cells are keeping track of the relative distance traveled rather than absolute position. This gives us evidence for the individual place cell’s ability to represent relative distances.”
Mehta thinks this is because the neuronal maps generated by three different categories of stimuli: distal cues, gait and stuff, are all competing for the control of neural activity. He said, “All the external stuff is fixed at the same absolute position and hence generates a representation of absolute space. But when all the stuff is removed, the profound contribution of gait is revealed, which enables neurons to compute relative distances traveled.” Dr. Mehta suggests that there are multiple maps of space in neuronal networks and they compete with each other to generate a full map.
The researchers also found a surprising discovery about the brain’s theta rhythm. It’s known that place cells use theta rhythm, the rhythmic firing of neurons, to keep track of “brain time,” the brain’s internal clock. Normally, said Dr. Mehta, the theta rhythm becomes faster as the subjects run faster, and slower as running speed decreases. This speed dependent change in the brain rhythm was thought to be crucial for generating the ‘brain time’ for place cells. But the researchers found that in the virtual world the theta rhythm was uninfluenced by running speed. He noted, “That was a surprising and fascinating discovery because the ‘brain time’ of place cells was unchanged and still as precise as that in the real world. This gives us a new insight about how the brain keeps track of space-time.”
The researchers found the spiking of place cells was very precise, down to one hundredth of a second, “so fast that we humans cannot perceive it but neurons can,” he said. “We have found that this very precise spiking of neurons with respect to ‘brain-time’ is crucial for learning and making new memories.” Dr. Mehta explained, all told, said Mehta, the results provide insight about how distinct sensory cues both cooperate and compete to influence the intricate network of neuronal activity.