Memories help animals make predictions. A honeybee may remember that the smell of orange blossoms means nectar is nearby. But sometimes memories require updating. “If you know that your fridge is a good source of food, and you go to the fridge a couple of times and there is nothing there, then you start to devalue the idea that the fridge is full of food,” says neurobiologist Scott Waddell of the University of Oxford in the United Kingdom.
Waddell and colleagues detailed the neural mechanisms underpinning how fruit flies update or maintain memories. Their work, which appeared in a recent issue of Nature, could improve therapies that attempt to block unwanted memories like those associated with post-traumatic stress disorder (PTSD).
The researchers began by offering fruit flies an odor followed by a sugar reward, then a second odor with no reward. Once the flies learned to connect the reward odor to sugar, the scientists presented one group of the flies with that odor again. But this time, no sugar followed. Three other groups of flies smelled the non-reward odor, a new odor, or no odor. Three hours later, the scientists tested whether flies preferred the original reward odor or the non-reward odor. They found that the group of flies that had most recently experienced the reward odor without the reward no longer connected the scent to sugar, a change that neuroscientists call “memory extinction.”
Waddell wanted to understand the neural mechanisms that underlie memory extinction and whether the memory was really gone. He already knew that memories of odors are encoded in a portion of the fruit fly brain known as the mushroom body. There, one set of dopamine-producing neurons writes memories of rewards, while another set writes memories of punishments. The team repeated their experiments while using a combination of temperature and light-sensitive transgenes to systematically shut down and stimulate different subsets of these neurons. They learned that the punishment-coding neurons recorded the missing sugar reward much as they would an actual punishment like a bitter taste or high heat. But the original memory of the odor linked to sugar also remained coded in the brain. “The aversive memory is competing with the original reward memory,” explains Waddell. The memories are both present, but essentially at a standoff, which results in no odor preference.
Waddell then wanted to understand how fruit flies maintain memories when predictions do turn out as expected—a process neuroscientists refer to as “memory reconsolidation.” He knew that each time an odor makes flies recall a stable long-term memory, the memory becomes temporarily labile before being restabilized after the prediction turns out to be true.
The team found re-exposing flies to the non-reward odor triggered a memory reconsolidation process that stabilized the memories of both it and the reward odor. But when they disrupted reconsolidation by giving flies a cold shock soon after re-exposing them to the non-reward odor, the flies forgot that the reward odor was associated with sugar. And this time, the original memory was actually lost instead of just neutralized by the new memory.
“This paper addresses really big questions for both invertebrate and vertebrate researchers in emotional memory, which is how these memories are represented in the brain and how behavioral responses are updated with additional experience,” says neuroscientist Roger Clem of the Icahn School of Medicine at Mount Sinai, who was not involved in the study. But Clem cautions that the neural circuitry of the fruit fly brain is quite different from the human one—human brains don’t have mushroom bodies. But humans do have dopamine-producing neurons in areas of the brain where memories are formed. “It is quite possible that there are similar pathways,” says Waddell.
If researchers could identify these neural pathways in humans, they might be able to develop more effective therapies to disrupt a traumatic memory during reconsolidation, he explains. “Then you could make it disappear forever.” Indeed, this sort of therapy has already been tested with some success in humans.