Scientists learn that memories are stored in other parts of the body, not just in the brain

We’ve all been told that many short study sessions beat one long, all-night “cramming” marathon. That basic idea – called the signal spacing effect – shows up again and again in memory research.

Here’s the twist: signs of this memory spacing effect don’t stop at the neurons in the brain.

A surprising lab study reveals that spacing out chemical signals also boosts both the strength and the memory of the response in everyday normal human cells, not just in neurons.

In addition, as with memory stored in the brain’s neurons, the pattern and the timing of the signals also matter for memory in other human cell types. Cellular responses to spaced burst signals last longer, even when the total signal is the same.

This study suggests that the same “learning rules” that apply for students in the classroom also apply down at the molecular level – an incredible concept, to say the least.

Studying spaced signals and memory

Researchers at New York University grew non-neural human cells in dishes and gave them a built-in “reporter” that briefly glows when a certain gene switches turn on.

The reporter used a short-lived form of firefly luciferase, which is controlled by a DNA element called a cAMP response element (CREB).

When the protein CREB is activated, the glow rises and then fades quickly, so the signal reports what’s happening now, not what happened earlier. Think of it like a live scoreboard for whether the cell’s “learning” machinery is currently engaged.

Next, they needed a way to “train” the cells. In animals, certain chemicals, like the neurotransmitter serotonin, can trigger the molecular cascades that help form long-term memories.

The researchers used two lab tools that hit parts of those same cascades: forskolin, which boosts a signaling pathway that activates an enzyme called protein kinase A (PKA), and a phorbol ester called TPA, which activates another enzyme called protein kinas C (PKC).

Those alphabet soups – CREB, PKA, PKC – are all proteins that pass messages inside cells and ultimately influence genes.

You can think of them as messengers that carry a beat from the outside world into the cell’s control room, where DNA decisions get made.

Spaced signals vs. massed signals

When the scientists gave the cells one big “massed” pulse of signal, the reporter lit up. But when they gave the cells several short pulses spaced by short breaks – four quick hits, separated by minutes – the glow was stronger and lasted longer.

The memory spacing effect held whether the scientists used the PKA route, the PKC route, or both. The cells weren’t just counting the total dose – they were reading the rhythm.

That behavior matches what memory studies have shown in animals and people for more than a century.

“This reflects the massed-space effect in action,” says Kukushkin, a clinical associate professor of life science at NYU Liberal Studies and a research fellow at NYU’s Center for Neural Science.

“It shows that the ability to learn from spaced repetition isn’t unique to brain cells, but, in fact, might be a fundamental property of all cells.”

In study after study, well-timed events can drive more durable memory changes than one long exposure. In cells, that “durable change” shows up as a longer-lasting boost in gene activity.

If that sounds like “learning,” that’s because at the molecular level, it kind of is. Learning in neurons depends on waves of activity that feed into CREB, which then turns on sets of genes that change how cells behave for hours or days.

Spacing signal patterns and memory

The biochemical circuits normal cells carry can integrate pulses over time and give a bigger, longer-lasting response to spaced signals than to massed signals.

Next, to figure out how this process actually works, the researchers looked upstream of CREB at another key player, ERK. It’s a protein kinase known to pulse in response to stimuli.

They found that spaced stimulation produced stronger and more sustained activation of ERK and CREB than massed stimulation did.

When the team blocked ERK or interfered with CREB, the spacing advantage disappeared. That result ties the effect to the same molecular players that have always been linked to long-term memory in neurons.

Real-world implications

Why does it matter? Because this discovery completely reframes “learning” as not only a brain trick, but also as a general principle of how cells process information over time.

Cells aren’t just on/off machines; they notice patterns – the number of pulses, the spacing between them – and they make computations with those patterns.

That idea has practical uses. Researchers and clinicians often focus on how much of a drug to give. Dose matters, but schedule can matter just as much.

In some cases, smaller amounts delivered in pulses could push cells toward stronger or more useful gene responses than a single large dose. Timing, therefore, becomes a real-world design tool.

Limits and next steps

As thorough as this research was, there are always limitations to consider.

This study used immortalized human cell lines, engineered “reporters,” and controlled stimuli. Real tissues juggle many signals at once and include feedback from nearby cells and the immune system. That complexity can shape how timing plays out.

However, even with those limits, these dish experiments highlight a clear point: you can see spacing rules inside single cells without any wiring.

That helps isolate which steps carry the timing information and suggests clear follow-ups, like testing different intervals, pulse numbers, or combinations of pathways in primary cells and organoids.

Spacing, memory, and human cells

To sum it all up, these scientists found that four short, properly spaced chemical pulses trigger stronger and more durable gene activation than one longer pulse in human cells.

This “spacing effect” lines up with higher, longer activation of ERK and CREB – two molecular players already known to be crucial for memory in neurons – and blocking ERK or CREB erases the advantage of spacing.

Spacing isn’t just a study habit. It’s a principle written into cell signaling. When signals arrive in well-timed bursts, cells can lock in a stronger, longer-lasting response than they do after one massed burst hit.

“Learning and memory are generally associated with brains and brain cells alone, but our study shows that other cells in the body can learn and form memories, too,” explains New York University’s Nikolay V. Kukushkin, the lead author of the study.

Kukushkin and his team proved that hallmarks of learning don’t require a brain or even a neuron – they can emerge from the timing-dependent dynamics of signaling networks that many cell types share.

That insight could help scientists build better models of memory, design smarter drug-dosing schedules, and explore “cellular cognition” as a broader biological principle.

The full study was published in the journal Nature Communications.

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