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Brain cells called microglia eat away mice’s memories

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Immune cells in the brain
chew up memories, a new study in mice shows.

The finding, published in
the Feb. 7 Science, points to a completely new way that the brain forgets, says neuroscientist Paul Frankland of the Hospital
for Sick Children Research Institute in Toronto, who wasn’t involved in the
study.

That may sound like a bad
thing, but forgetting is just as important as remembering. “The world
constantly changes,” Frankland says, and getting rid of unimportant memories —
such as a breakfast menu from two months ago — allows the brain to collect
newer, more useful information.

Exactly how the brain stores memories is still debated, but many scientists suspect that connections between
large groups of nerve cells are important (SN:
1/24/18). Forgetting likely involves destroying or changing these large
webs of precise connections, called synapses, other lines of research have
suggested. The new result shows that microglia, immune cells that can clear
debris from the brain, “do exactly that,” Frankland says.

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Microglia are master brain
gardeners that trim extra synapses away early in life, says Yan Gu, a
neuroscientist at Zhejiang University School of Medicine in Hangzhou, China. Because
synapses have a big role in memory storage, “we started to wonder whether
microglia may induce forgetting by eliminating synapses,” Gu says.

Gu’s team first gave mice an
unpleasant memory: mild foot shocks, delivered in a particular cage. Five days
after the shocks, the mice would still freeze in fear when they were placed in
the cage. But 35 days later, they had begun to forget and froze less often in
the room.

Next, the researchers used a
drug to get rid of microglial cells in some mice’s brains. Mice with fewer
microglia froze more in the cage than mice with normal numbers of microglia,
indicating that those rodents held on to the scary memory. The same was true of
mice with microglia that, thanks to a drug, were unable to gobble up synapses.
Those mice also seemed to hold on to the memory, the researchers found.

The study also hints at which
memories are particularly vulnerable. Scientists marked the nerve cells that
stored the fearful memory with a glowing dye and gave the mice a drug that kept
these memory-holding cells silent, unable to fire off signals. These unused,
silent memories seemed to be more susceptible to microglia. That finding suggests
that “less-revisited memories are easier to remove,” Gu says.

The results come from one
particular type of memory: a fearful one, and one that’s stored in the
hippocampus. That brain structure is thought to be an early, temporary stop
before memories move to longer-term storage. Researchers don’t yet know whether
microglia would have a similar effect on memory-related synapses elsewhere in the
brain. Microglial synapse-culling has been tied to the early stages of Alzheimer’s disease (SN: 3/31/16).

Also unclear is why some old memories — ones not recalled for years — survive.
The related synapses may be extra durable, or maybe those memories are stored
where microglia are less active, Gu says. Or perhaps people do revisit these
memories and keep them strong, even if they’re not aware of it.

Other overlapping
explanations for forgetting exist, such as the behavior of certain proteins and
the creation of new nerve cells, as Frankland’s work has suggested (SN: 5/8/14). These ideas involve
synapses changing with time. “All of these could conceivably be natural
forgetting mechanisms,” Frankland says.

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