The first dance I did at my wedding was exactly four minutes and 52 seconds long. But it’s something that I will remember for many decades. Neuroscientists still don’t entirely understand this: How was my brain able to translate this less-than-five-minute experience into a lifelong memory? The puzzle lies in the gap between memory and experience: Our experiences are brief, but it can take hours to create a long-term mental image.
My colleagues and I recently published a paper in the journal Neuron that explains how the brain maintains temporary molecular memories of transient experiences. This discovery not only helps explain how the brain bridges between experience and memory. This allows us to read short-term memories in the brain, which could one day allow us to deduce a person’s past experiences – or even a lab mouse’s – by simply looking at their brain molecules.
Electrical pulses are sent along the branches of neurons. Santiago Ramon y Cajal, CC BY
Experience the thrill of a lifetime.
We began by asking the brain how it records electrical activity. Each experience, whether it’s chatting with a buddy or smelling French fries, is associated with its unique pattern in the brain and nervous system. These patterns of activity are determined by the neurons that are active and how they are functional.
You’re lifting weights at the gym. It’s easy to tell which neurons are active: If you lift with your right hand, you will have different neurons than if your left arm is lifted. This is because the neurons of each component are other.
In contrast, the way a neuron functions is infinitely flexible. The electrical activity of neurons can take on any pattern you can think of over time. Electrical activity can be varied in terms of duration or whether it occurs in clumps. Lifting a heavier load will result in more heartbeats per minute.
It’s the combination of which neuronal activity is active, and their frequency of pulsing that determines how you feel when lifting a 10-pound weight in your right hand compared to a 5-pound weight in your left.
Neurons activate genes.
We couldn’t test all possible patterns of electrical activity in our experiments, so we concentrated on how neurons measure the length of time they are active.
We predicted that they would keep these records if we turned on genes. In their DNA, all the cells of your body contain the same genes. Different genes are activated depending on what type of cell it is and the experiences that it has had in its lifetime. The genes that are active in a cell make it unique.
Researchers have known for about 30 years that neurons activate certain genes if they are electrically active. When a gene is activated in a neuron, the cell sends a Molecular Xerox to the gene’s location in DNA. The molecular Xerox creates many copies of the gene as new molecules. These molecules are not made from DNA but instead the closely related RNA. These RNA molecules can remain in cells for up to a few days, and they serve as a record of the brain’s activity.
We wanted to know if the genes in neurons could record the activity of the neurons, not only the fact that they were active at all but also how they were active. Do neurons that have been activated for different periods – longer or shorter, for example – turn on a foreign gene?
We predicted that they would. Long-term memory is stored in the physical changes of the neurons, and the type change is determined by electrical activity patterns the neuron experiences. We predicted that in order for the brain to create lasting changes, it would need to track not just which neurons are active but also how they are functional.
Researchers activated mouse neuronal growth in a dish. Kelsey Tyssowski,
In our experiments, we exposed mouse neurons that were growing in a petri dish to a chemical that turned them on. The neurons were active as long as the chemical remained in the word. We could keep them on for a variety of times.
In fact, we found that neurons activated in a dish for different periods turned on other genes. This genetic record-keeping system is surprisingly simple: the longer neurons are activated, the more genes turn on.
It turned out that this was true for neurons growing in a petri dish as well as in the brains of living mice. We were able, by exposing mice with bright lights to the vision centers in their brains, to activate those neurons for as long as they were lit. The longer the light shone, the greater the number of genes that were started and their RNA copies in the cell. The molecules in a neuron are different in those that were active briefly and in those that had been active for some time.