The baby zebrafish measures only half of the length of a regular pea. A recent look inside its transparent brain, however, offers clues to the far bigger mystery of how we remember—and how we forget.
Researchers from the University of Southern California showed the little fish how to respond to heat and light. Using a custom-designed microscope, the team then captured images of the animals’ brains in the moments before and after they learned to associate the light and the heat. It’s the first known look at how a living vertebrate’s brain restructures itself as the animal forms a memory.
A living Zebrafish larva’s brain. These small dots, which are green and white in color, represent synaptic connections before the exercise.
Zhuowei Du
In the image published with the team’s research, the event looks like a dissipating firework. Bright yellow dots are forming new connections between brain cells in the same moment that memory was formed. But the image also shows a second, parallel force at work in the animal’s brain as those connections are made. The synaptic connections are represented by a series of dots in bright blue that overlap. It is as though the old components of zebrafish memories have been lost and the new ones were formed simultaneously.
Illustration of synaptic changes that occur when memory is created. Each dot is a new connection; every dot is a loss.
William Dempsey, Anna Nadtochiy
This glimpse into the mind of a zebrafish illuminates one of the most intriguing new fronts in science’s quest to understand the brain: the biology of forgetting.
We often experience forgetting as a frustration—the misplaced wallet, the name just on the tip of your tongue. The widely accepted convention in neuroscience held that forgetting is a memory glitch. The brain’s job was to gather and store information, and the inability to retain or retrieve those memories was a failure of some neurological or psychological mechanism. Science has shown that forgetting does not simply result in a loss of memories, but is a distinct phenomenon.
“We were all taught forever, everyone, that forgetting is a passive breakdown of the memory mechanisms,” says Scott A. Small is a Columbia University professor of neurology and psychiatrist and the author of 2021. Not remembering: How to forget. “The fundamental insight—the eureka, I think, of the new science of forgetting—is that our neurons are endowed with a completely separate set of mechanisms … that are dedicated to active forgetting.”
The brain forms memory with the help of a complex tool kit of neurotransmitters, proteins, and carbohydrates, as well as other cells, Small writes; forgetting, too, has its own set of dedicated molecular tools working to clear away what’s no longer relevant.
The mere existence of these neurobiological tools doesn’t prove that they’re useful; nature also gave us the appendix, and we’re still trying to figure out what the point of that one is. But a “constellation of findings” in recent years, Small says, indicates that culling the vast amount of information the brain collects and encodes is a necessary function of cognition—as essential for survival as the gathering of useful knowledge. Now that this function is known, researchers have begun to explore the possibility of disrupting forgetting in order to gain insight into psychological conditions such as post-traumatic stress disorder.
After all, forgetting, says Oliver Hardt, an assistant professor of psychology at McGill University, is “one of the most fundamental aspects of a memory system. Without forgetting, nothing would work.”
The Nobel Prize–winning neuroscientist Eric Kandel, a professor of biochemistry and biophysics at Columbia University, established in the 1970s that changes in the chemical signals between neurons were the biological basis of all learning or memory making.
When neighboring brain cells, or neurons, are excited at the same time, neurotransmitter chemicals fire across the microscopic gap between the ends of the neurons’ spindly dendrites. This change in the synapse—the connection point—between neurons is what makes a memory. This change in the synapse-the connection point between neurons –is what makes a memory. It is temporary for short-term memories. However, the more that a memory can be retold and repeated over and again, the more durable and lasting it becomes. That’s true of all animals capable of learning, Kandel found, from humans to the humble zebrafish. (“Practice makes perfect,” Kandel said in his Nobel lecture, “even in snails.”)
If all animal brains are capable of forming new synaptic connections, it stands to reason that they’re also equipped to pare those connections away. This picture of the brain of a zebrafish illustrates how it is possible to create new synaptic links between certain neurons while also receding those between other neurons.
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From an evolutionary perspective, the purpose of memory “is not to allow us to sit back and say, ‘Oh, do you remember that time?’” says Sheena Josselyn, a senior scientist at the Hospital for Sick Children, and a professor of psychology and physiology at the University of Toronto. “It really is to help us make decisions.”
Hardt says that without forgetting the evolutionary advantages of having a good memory, it would be redundant. In a single day the brain records hundreds of thousands upon hundreds of thousands of pieces of information. Some are relevant but many of them irrelevant. For example, how the socks feel on your feet when they’re on, or the shirt color of the stranger in line at the grocery store.
“You would have an endless amount of useless stuff accumulating there constantly,” Hardt says. “And each time you want to think about something”—something key to your survival, such as the location of food or the signs of an approaching predator—“all these memories would pop up that are completely meaningless and that make it hard for you to actually do the job of predicting what is next.”
Hardt is just one of many scientists to suspect that sleep is a key function. A good night’s sleep quite literally produces a clearer mind.
Josselyn and her spouse Paul Frankland run the Josselyn Frankland Neurobiology Lab at Toronto’s Hospital for Sick Children. Frankland’s research at the hospital has focused on the kind of forgetting that takes place in the hippocampus when new learning takes place—the corresponding gain and loss of neuronal connections that the zebrafish brain showed.
Frankland’s breakthrough in forgetting came while he was studying neurogenesis, or the formation of new brain cells, in mice. A graduate student noticed that the more quickly new neurons formed in the animal’s hippocampus, the less likely the animal was to recall some older memories. Not only did mice learn new mazes quicker, but also they were more likely to forget how they had previously mastered mazes before brain development.
Frankland has theorized that’s why it’s so difficult for people to remember events from early infancy, a time of exponential neural development. In this model, forgetting in the hippocampus isn’t a zero-sum, one-for-one replacement of knowledge, so much as an ongoing reconfiguring of memory so that more recent (and likely, more useful) information is available more readily. “The world changes,” Frankland says, “and so the more recent things are more relevant to remember to predict the future than the more distant things.”
Just as the brain’s cells and circuits distinguish between long- and short-term memory, there also appears to be a distinction between memories that have decayed beyond the possibility of retrieval and what researchers call “transient” forgetting—the temporary (if deeply irritating) inability to recall a piece of learned information.
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Studies in fruit flies, most notably in the Scripps Research Institute lab of neuroscience professor Ronald L. Davis, have identified dopamine as a key factor in the animals’ ability to learn and forget. Last year, the lab found a dopamine-releasing circuit in the flies’ brains linked to transient forgetting. Flies that had been taught to associate a particular odor with a shock to their feet seemed to forget what they’d learned when distracted by stimuli like blue light or a puff of air. The temporary loss in memory was caused by dopamine being released from certain cells to the cells believed to have memory.
Fruit flies may have an ability to temporarily suppress some memories. It stands to reason that humans might also be able this mechanism. “Forgetting may be the basal state of the brain. We are inundated with so much information on a daily basis that the brain fights back and says, ‘I can’t handle this. I need to forget as much of the unimportant information as possible,’” Davis says. “The brain is designed to slowly erase information that’s coming in on a daily basis unless consolidation says, OK, this memory is important. And so it overrides the forgetting mechanism.”
Some researchers question whether forgetting mechanisms might hold clues to cognitive or behavioral health. Small identifies a handful of key areas where the neuroscience behind forgetting could lead to breakthroughs. Autism is one area of particular interest. In one 2016 study, when a protein associated with forgetting was inhibited in fruit flies, those that had been modified to contain genes linked to autism demonstrated “behavioral inflexibility,” or difficulty adopting new patterns of behavior. Small believes that autism spectrum disorder sufferers may be unable to accept excessive stimuli.
A similar possibility could lead to post-traumatic stress disorder. One hypothesis is that PTSD results from an increased number of synaptic links in the amygdala. The brain’s part that stores fear memories and creates them after repeated or intense exposure to a scary stimulus. Early studies show that drugs that accelerate the loss of fear memories—most notably, MDMA—could be effective in treating the symptoms of people with PTSD.
The memory loss associated with Alzheimer’s disease and other forms of dementia ranges far beyond the kind of routine forgetting that takes place in a healthy brain. Understanding the mechanism behind this painful and often fatal symptom could aid researchers in understanding how to stop or slow it down.
“Perhaps we need to understand the forgetting process, how that works, why it is there, in order to find a better way to address it if it goes out of control,” Hardt says.
Several researchers interviewed for this piece referenced the Jorge Luis Borges short story “Funes the Memorious” to illustrate forgetting’s role in how we navigate the world.
A riding accident injury leaves Funes with chronic memory loss. Funes learns multiple languages with ease and can cite millennial–long strings of historical facts—the kinds of things we think we’d do with infinite capacity for recall. But he’s miserable. Funes can’t let go of anything. He looks at a landscape and registers every leaf on the vines, every hair in a pony’s mane. He’s swamped by minute changes of age and expression each time he looks at another person’s face. Memories don’t comfort him; they only overwhelm. “My memory, sir, is like a garbage heap,” Funes tells the narrator.
We can forget. This helps us to focus on what is important and tunes out unnecessary information. It is essential to avoid anger and grief. However, feelings of love, attraction, and sadness would never go away, which makes it difficult to get on with your life. Forgetting is a way to remove the unnecessary, which shapes our perceptions of ourselves and the world around us.
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