Study highlights how the brain encodes time and place into memories

Studies could lead to new ways to enhance memory for those with traumatic brain injury or Alzheimer's disease.


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Almost a decade ago, neuroscientists discovered a group of neurons called time cells in the brain’s hippocampus region in rats. Scientists found that these time cells play a vital role in the recording when events occur, allowing the brain to mark the order of what happens in episodic memory correctly.

These cells show a characteristic activity pattern while the animals are encoding and recalling events. By firing in a reproducible sequencing, they allow the rain to organize when occasions occur. The timing of their firing is constrained by 5 Hz brain waves, called theta oscillations, in a process known as precession.

Bradley Lega, M.D., associate professor of neurological surgery at UTSW, demonstrated whether humans also have time cells using a memory task that makes strong demands on time-related information. In two studies, scientists shed new light on how the brain encodes time and place into memories.

The study recruited volunteers from the Epilepsy Monitoring Unit at UT Southwestern’s Peter O’Donnell Jr. Brain Institute, where epilepsy patients stay for several days before surgery to remove damaged parts of their brains spark seizures. Electrodes implanted in these patients’ brains help their surgeons precisely identify the seizure foci and also provide valuable information on the brain’s inner workings.

Scientists recorded the brain’s electrical activity from the hippocampus in 27 volunteers’ brains during ‘free recall’ tasks. The tasks involved reading a list of 12 words for 30 seconds, doing a short math problem to distract them from rehearsing the lists, and then recalling as many words from the list as possible for the next 30 seconds.

For the task, volunteers need to associate each word with a segment of time (the list it was on), which allowed Lega and his team to look for time cells. The outcomes were astonishing: Not only did they identify a robust population of time cells, but the firing of these cells predicted how well individuals were able to link words together in time (a phenomenon called temporal clustering). Finally, these cells appear to exhibit phase precession in humans, as predicted.

Lega said, “For years, scientists have proposed that time cells are like the glue that holds together memories of events in our lives. This finding specifically elegantly supports that idea.”

In another study, Brad Pfeiffer, Ph.D., assistant professor of neuroscience, led a team investigating place cells- a population of hippocampal cells in animals and humans that records where events occur.

It is well known that animals travel through a path they have been before- neurons encoding different locations along the path will fire in sequence, much like time cells fire in the order of temporal events. 

When rats explore their surroundings, the place cells are organized into “mini-sequences” that represent a virtual sweep of locations ahead of the rat. These radar-like sweeps happen roughly 8-10 times per second and are thought to be a brain mechanism for predicting upcoming events or outcomes.

When rodents quit running, place cells would often reactivate in long sequences that seemed to replay the rat’s prior experience in reverse. While these “reverse replay” events were known to be significant for memory formation, it was unclear how the hippocampus had the option to produce such successions. To be sure, substantial work has shown that experience ought to strengthen forward, “look ahead” sequences; however, debilitate turn around replay events.

To determine how these backward and forward memories work together, scientists placed electrodes in rats’ hippocampi. They then allowed the rats to explore two different environments: a square arena and a long, straight track. To encourage them to move through these spaces, they placed wells with chocolate milk at various places. They then analyzed the animals’ place cell activity to see how it corresponded to their locations.

Particular neurons fired as the rats wandered through these spaces, encoding information on the place. These same neurons fired in the same sequence as the rats retraced their paths and periodically fired in reverse as they completed different legs of their journeys. 

However, taking a closer look at the data, the researchers found something new: As the rats moved through these spaces, their neurons not only exhibited forward, predictive mini-sequences, but also backward, retrospective mini-sequences. The forward and backward sequences alternated with each other, each taking only a few dozen milliseconds to complete.

Pfeiffer said, “While these animals were moving forward, their brains were constantly switching between expecting what would happen next and recalling what just happened, all within fraction-of-a-second timeframes.”

Scientists are now studying what inputs these cells receive from other parts of the brain that cause them to act in these forward or reverse patterns.

Theoretically, it is possible to hijack this system to help the brain recall where an event happened with more fidelity. Likewise, stimulation techniques might eventually mimic the precise patterning of time cells to help people more accurately remember temporal sequences of events.

Lega said“In the past few decades, there’s been an explosion in new findings of memory. The distance between fundamental discoveries in animals and how they can help people is becoming much shorter now.”

Journal References:
  1. Mengni Wang, David J. Foster, Brad E. Pfeiffer. Alternating sequences of future and past behavior encoded within hippocampal theta oscillations. Science, 2020; 370 (6513): 247 DOI: 10.1126/science.abb4151
  2. Gray Umbach, Pranish Kantak, Joshua Jacobs, Michael Kahana, Brad E. Pfeiffer, Michael Sperling, Bradley Lega. Time cells in the human hippocampus and entorhinal cortex support episodic memory. Proceedings of the National Academy of Sciences, 2020; 117 (45): 28463 DOI: 10.1073/pnas.2013250117


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