The secret to lasting memories? It’s simply a matter of brain energy

Why do some memories stick, while others fade away?

Some experiences leave a lasting impression on us, while others disappear before the sun even rises. How can we explain this sorting process carried out by our brains? A new study suggests that the answer may lie not in emotion or repetition, but in a simple burst of energy at a crucial moment.

Researchers have indeed discovered a fascinating mechanism: by slightly prolonging the activation of mitochondria—the structures that produce energy inside our neurons—it is possible to transform a fleeting memory into a lasting one. This discovery places brain energy at the heart of the memory-forming process, far beyond its simple role as a background fuel source.

By extending a natural calcium signal in nerve cells, the team of scientists succeeded in stimulating cellular energy production at a critical moment. The result is striking: the test animals were able to form long-term memories after a single learning event. The timing of energy production could therefore be one of the decisive factors determining which memories we retain.

Extending the Energy Surge: A Targeted Intervention

In the neurons involved in memory, the process is normally brief. Mitochondria take up calcium when the cell is active, then rapidly release it, bringing energy production back to its baseline level. The team led by Jaime de Juan-Sanz at the Paris Brain Institute (ICM) demonstrated that slowing down this release phase allows calcium to linger, thereby maintaining high energy production well beyond the initial burst of activity.

The trick was not to flood the cells with more calcium, but simply to prolong a natural signal that normally fades within a few seconds. To achieve this, the researchers targeted a calcium efflux pathway that shuts down mitochondrial energy production. This pathway depends on a protein called LETM1, whose role is precisely to remove calcium from the mitochondria and return them to their resting state.

By blocking the action of the LETM1 protein, they were thus able to slow the release of calcium. The mitochondria remained stimulated for longer, even after the neurons had stopped firing. Thanks to this persistent calcium, key enzymes remained active, continuing to convert fuel into ATP—the molecule cells use to perform their functions. This extra ATP didn’t make all thoughts faster, but it provided the sustained energy needed for certain stages of memory consolidation to be completed.

A finding validated in both insects and mammals

The effect of this manipulation was first observed in fruit flies. Normally, when a smell is associated with a mild punishment, the memory of this lesson fades within a few hours and disappears in less than a day. But when the team targeted neurons in the pedunculate body—the cells that store olfactory memories in the fly—a single lesson was enough to create a memory that lasted more than 24 hours.

Usually, only spaced-out training sessions force flies to invest in long-term storage. Here, simply stimulating energy production was enough to produce a lasting memory after a single session. Building on this success, the researchers tested the same mechanism in mice. Thirsty mice were trained to avoid an odor associated with an injection that induced nausea.

Ten days later, mice in which the LETM1 protein had been knocked out still avoided the aversive odor. In contrast, animals in the control group drank indifferently from both bottles. Importantly, the locomotion and water intake of the genetically modified mice remained normal, ruling out a simple change in motivation. The observation of an identical extension of memory in insects and mammals suggests the existence of a shared energy-control system that has been conserved throughout evolution.

The Energy Cost of a Long-Term Memory

However, not all types of memory were affected by this manipulation. Short-term memories, which normally fade within a few hours, continued to follow their usual course, even when the mitochondria retained calcium for longer during learning. The reason is simple: long-term storage is an energy-intensive process.

It requires hours of additional cellular work, including the production of new proteins and the reorganization of synaptic connections. This prolonged effort demands sustained energy that the initial surge does not always provide. As Jaime de Juan-Sanz explains: “It seems that our manipulation does not indiscriminately improve all forms of memory, but specifically those that require sustained energy investment.”

To put this into perspective, it’s important to note that the human brain, although it accounts for only about 2% of body weight at rest, consumes nearly 20% of the body’s total energy. Neurons constantly pump ions, recycle signaling molecules, and reset their connections. This study suggests that energy is not merely a background fuel, but that it may act as a true gatekeeper, deciding which experiences merit the investment needed to become a lasting memory.

A Promising Hope, but a Long and Complex Road Ahead

Despite these encouraging results, the path to human application is still fraught with challenges. Excessive calcium buildup inside mitochondria can damage neurons, meaning that any attempt to prolong this signal must remain within strict safety limits. Furthermore, the LETM1 protein is also implicated in Wolf-Hirschhorn syndrome, a rare genetic disorder, which directly links this molecular target to risks to human health.

It is crucial to note that this study used genetic knockout, not a drug, which does not pave a clear path toward memory-enhancing pills. Careful testing will need to be conducted at the ICM to determine precisely when an energy boost is beneficial, when it becomes harmful, and which brain circuits can tolerate such a change. Ideally, this energy boost should be activated only at key moments, after which the mitochondria would return to their normal state.

One avenue being explored is optogenetics, a technique that uses light-sensitive proteins to control cells, thereby activating or pausing mitochondrial calcium signals in selected neurons. Published in the journal Nature Metabolism, this research challenges our previous assumptions about the limits of learning and offers a new tool for testing how cellular energy defines the boundaries of our memory.

Source: earth.com

The secret to lasting memories? It’s simply a matter of brain energy