Time Cells and Episodic Memory in Humans


Let us not launch the boat ...
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The abstract, from Umbach, et al., 2020:

The organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, evidence accumulated over the last decade suggests that populations of “time cells” in the hippocampus encode temporal information. We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of retrieved memory items. We also uncover evidence of ramping cell activity in humans, which represents a complementary type of temporal information. These findings establish a cellular mechanism for the representation of temporal information in the human brain needed to form episodic memories.

The PNAS presentation includes a statement of significance:

Time cells are neurons in the hippocampus and entorhinal cortex that fire at specific moments within a cognitive task or experience. While many prominent theories of memory encoding offer time cells as the source of the temporal component to memory, they have never been observed in human recordings. We identify time cell populations in the medial temporal lobe of humans during memory encoding and retrieval. Further, we demonstrate that the stability of the time signal provided by time cells during encoding influences the ability to temporally order memories at time of retrieval.

This feels like it should be a big paper, which is also an easy overstatement for an armchair. Still: "a cellular mechanism for the representation of temporal information in the human brain needed to form episodic memories". That really does sound not simply like a neat technical accomplishment, but also an actual threshold with myriad possibilities beyond; that is, not simply a milepost but also a fundamental scientific access point to diverse pathways for future research. To the other, if this isn't the paper that is going to be remembered, what is?

The reality of what comes next is likely considerably more boring than anything dazzled imagination might come up with. But, really, it feels like they just said they found a cellular mechanism for time-stamping our memories, lending to proper recall. And, yeah, that feels like something big.


Umbach, Gray, et al. "Time cells in the human hippocampus and entorhinal cortex support episodic memory". Proceedings of the National Academny of Sciences. 27 October 2020. PNAS.org. 28 December 2020. http://bit.ly/34RRThb
"point to diverse pathways for future research."
pardon the pun

To me something bigger than time cells would be controlled reversion of general cells back to stem cells--I guess back to near embryonic state--in order to reverse aging.
Brainless Slime molds can memorize time intervals.

How Brainless Slime Molds Redefine Intelligence
Single-celled amoebae can remember, make decisions and anticipate change, urging scientists to rethink intelligent behavior. By Ferris Jabr on November 7, 2012
Gardeners sometimes encounter them in their backyards—spongy yellow masses squatting in the dirt or slowly swallowing wood chips. Hikers often spot them clinging to the sides of rotting logs like spilled bowls of extra cheesy macaroni. In Mexico some people reportedly scrape their tender bodies from trees and rocks and scramble them like eggs. They are slime molds: gelatinous amoebae that have little to do with the kinds of fungal mold that ruin sourdough and pumpernickel. Biologists currently classify slime molds as protists, a taxonomic group reserved for "everything we don't really understand," says Chris Reid of the University of Sydney.
Something scientists have come to understand is that slime molds are much smarter than they look. One species in particular, the SpongeBob SquarePants–yellow Physarum polycephalum, can solve mazes, mimic the layout of man-made transportation networks and choose the healthiest food from a diverse menu—and all this without a brain or nervous system. "Slime molds are redefining what you need to have to qualify as intelligent," Reid says.
This video was produced through a collaboration between NOVA and Scientific American. To learn more about slime molds and other amazing creatures, watch 'What Are Animals Thinking?' on NOVA scienceNOW, airing November 7, 2012 at 10 pm on PBS.
In the early 2000s Toshiyuki Nakagaki, then at Hokkaido University in Japan, and his colleagues chopped up a single polycephalum and scattered the pieces throughout a plastic maze. The smidgens of slime mold began to grow and find one another, burgeoning to fill the entire labyrinth. Nakagaki and his teammates placed blocks of agar packed with nutrients at the start and end of the maze. Four hours later the slime mold had retracted its branches from dead-end corridors, growing exclusively along the shortest path possible between the two pieces of food.
This past October Reid and his colleagues published a study revealing that the way a slime mold navigates its environment is even more sophisticated than previously realized. As polycephalum moves through a maze or crawls along the forest floor, it leaves behind a trail of translucent slime. Reid and his teammates noticed that a foraging slime mold avoids sticky areas where it has already traveled. This extracellular slime, Reid reasoned, is a kind of externalized spatial memory that reminds polycephalum to explore somewhere new.
Navigating a maze is a pretty impressive feat for a slime mold, but the protist is in fact capable of solving more complex spatial problems: Inside laboratories slime molds have effectively re-created Tokyo's railway network in miniature as well as the highways of Canada, the U.K. and Spain. When researchers placed oat flakes or other bits of food in the same positions as big cities and urban areas, slime molds first engulfed the entirety of the edible maps. Within a matter of days, however, the protists thinned themselves away, leaving behind interconnected branches of slime that linked the pieces of food in almost exactly the same way that man-made roads and rail lines connect major hubs in Tokyo, Europe and Canada.
Another set of experiments suggests that slime molds navigate time as well as space, using a rudimentary internal clock to anticipate and prepare for future changes in their environments. Tetsu Saigusa of Hokkaido University and his colleagues—including Nakagaki—placed a polycephalum in a kind of groove in an agar plate stored in a warm and moist environment (slime molds thrive in high humidity). The slime mold crawled along the groove. Every 30 minutes, however, the scientists suddenly dropped the temperature and decreased the humidity, subjecting the polycephalum to unfavorably dry conditions. The slime mold instinctively began to crawl more slowly, saving its energy.
After a few trials, Saigusa and his colleagues stopped changing the slime mold's environment, but every 30 minutes the amoeba's pace slowed anyway. Eventually it stopped slowing down spontaneously. Slime molds did the same thing at intervals of 60 and 90 minutes, although, on average, only about half of the slime molds tested showed spontaneous slowing in the absence of an environmental change.
Because the slime mold cannot rely on its slime for this trick, Saigusa speculates that it instead depends on an internal mechanism of some kind, perhaps involving the perpetually pulsating gelatinous contents of its one cell, known as cytoplasm. The slime mold's membrane rhythmically constricts and relaxes, keeping the cytoplasm within flowing. When the amoeba's membrane encounters food, it pulsates more quickly and expands, allowing more cytoplasm to flow into that region; when it stumbles onto something aversive—such as bright light—its palpitations slow down and cytoplasm moves elsewhere. Somehow, the slime mold may be keeping track of its own rhythmic pulsing, creating a kind of simple clock that would allow it to anticipate future events.
P. polycephalum is not only a great navigator and good forward thinker, so to speak—it is also a healthy eater. Slime molds survive best on a diet comprising two thirds protein and one third carbohydrates. Audrey Dussutour of the University of Paul Sabatier in France placed slime molds in the center of a clock face of 11 different pieces of food, each with a unique ratio of proteins and carbohydrates. When presented with this circular menu, slime molds consistently glommed onto the piece of food with optimal balance of nutrients.
Compared with most organisms, slime molds have been on the planet for a very long time—they first evolved at least 600 million years ago and perhaps as long as one billion years ago. At the time, no organisms had yet evolved brains or even simple nervous systems. Yet slime molds do not blindly ooze from one place to another—they carefully explore their environments, seeking the most efficient routes between resources. They do not accept whatever circumstances they find themselves in, but rather choose conditions most amenable to their survival. They remember, anticipate and decide. By doing so much with so little, slime molds represent a successful and admirable alternative to convoluted brain-based intelligence. You might say that they break the mold.

Forgive the verbose quotes, but this remarkable organism can teach us a great deal, due to its age and evolutionary continuity, which has refined into some remarkable adaptive abilities.