We all have memories that we treasure and return to often: the face of a loved one, a happy experience; an achievement. We also have memories that we may treasure emotionally but don't often revisit in our mind's eye. Those are the memories we're most likely to lose over time. Recently, scientists discovered that the process of forgetting is linked to cells in the brain that clear memories away, whether we want them to or not.
A mouse study published Wednesday in the journal Science presents evidence that microglia, a type of immune cell in the brain, essentially operates as a memory cleanup crew. Microglia help the brain in the act of "gradual forgetting" by eroding the neural circuitry that underpins our memories, explains Yan Gu, a neurobiologist at the Zhejiang University School of Medicine in China and the study's senior author.
If that process sounds scary, remember that forgetting is natural. The brain is constantly pruning away memories that it deems no longer useful, especially during REM sleep. In this case, the team suggests that microglia are the cells that help that process get started. But crucially, this slow forgetting only happens to certain kinds of memories — ones that you don't need anymore.
"According to our study, microglia remove synapses depending on the activity. That means, microglia likely remove memories that are not frequently revisited, no matter if these memories are wanted or unwanted," Gu tells Inverse.
A mouse memory isn't exactly like a human but their brains can serve as helpful models. In the experiment, the team looked for a simple way that we might be able to investigate the role that microglia play in memory. To do that, they tapped into mouse fear memories.
During a conditioning stage, mice were put in a box where they received mild foot shocks, which in turn, would be enough to make anyone freeze (how mice display fear) when they were put inside. Naturally, five days after they learned to fear the shocks, mice froze immediately when they were put inside.
After 35 days, the mice started to freeze less frequently, as their memories of pain faded. The team suggests that this forgetting was due to the microglia at work: The mice no longer needed their fear memories, so they were slowly forgotten.
To test whether it really was microglia were helping that memory fade the team injected a separate group of mice with a toxin that depleted the microglia in their brains. Those mice were significantly more likely to freeze after 35 days. Because of that difference, the team argues that this disparity shows that microglia are primarily behind the natural erosion of old memories.
Importantly, this study doesn't deal with the accelerated loss of memory (think: dementia), though microglia have also been involved in Alzheimer's research in the past. Microglia are cells in the brain that seek out pathogens and destroy them, and when they're activated in an unwarranted fashion, they could cause more harm than good.
But this experiment was focused on healthy forgetting, where microglia seem to be fulfilling a natural role. While that may seem like something we would like to avoid, there are reasons why it exists and also, ways to make sure your most useful memories stay intact.
Why do we lose our memories?
Gu explains that microglia appear to target engrams, which are permanent biological changes in the brain that occur when a memory is formed. They've been described as "units" of memory, but Gu describes them more like treasure maps.
"Memory can be retrieved when related engram cells are activated, just like we can figure out the location of the treasures when we find out all the clues in the treasure map," he says. "Memory information cannot be retrieved if some of the engram cells do not activate — like we cannot find the treasure if some clues are missing."
Microglia, this paper suggests, may actually remove the paths between some of those clues in the brain. Specifically, the team suggests that they target synapses – connections between brain cells – that are formed and strengthened as we learn new things, or form strong, new memories.
"We cannot find the treasure if some clues are missing."
Over time, though, we just may not need those memories anymore. If you change jobs, you may not need to remember the same back-road short cut you took the office. If the kid who bullied you in elementary school isn't in your life anymore, you may not need to remember their name.
That's why Gu suggests that microglia target "remote" memories. Microglia are efficient if nothing else. Though you may feel emotionally attached to a memory you've kept buried away, if you don't revisit it often, microglia are likely to see if as non-relevant.
"To microglia, if the memory is not revisited at all, it may be an outdated memory that may not be wanted later and should be cleared out, although pruning of this memory might be “unwanted” by ourselves," says Gu.
"That means, if we learn something and don’t want to forget, we will have to revisit it repetitively to make the memory cells active so that the microglia will not prune these memories."
If you do have a memory you're looking to keep salient, the best thing you can do is visit that memory often: — whether that's a face of a loved one, a treasured experience or a skill. Reminding the cells in your brain why that memory formed, and why it's important or useful to you could help keep it around, says Gu.
Abstract: Synapses between engram cells are believed to be substrates for memory storage, and the weakening or loss of these synapses leads to the forgetting of related memories. We found engulfment of synaptic components by microglia in the hippocampi of healthy adult mice. Depletion of microglia or inhibition of microglial phagocytosis prevented forgetting and the dissociation of engram cells. By introducing CD55 to inhibit complement pathways, specifically in engram cells, we further demonstrated that microglia regulated forgetting in a complement- and activity-dependent manner. Additionally, microglia were involved in both neurogenesis-related and neurogenesis-unrelated memory degradation. Together, our findings revealed complement-dependent synapse elimination by microglia as a mechanism underlying the forgetting of remote memories.