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Memory Trace in Mouse Hippocampus

Credit:Sahay Lab, Massachusetts General Hospital, Boston

Play the first few bars of any widely known piece of music, be it The Star-Spangled Banner, Beethoven’s Fifth, or The Rolling Stones’ (I Can’t Get No) Satisfaction, and you’ll find that many folks can’t resist filling in the rest of the melody. That’s because the human brain thrives on completing familiar patterns. But, as we grow older, our pattern completion skills often become more error prone.

This image shows some of the neural wiring that controls pattern completion in the mammalian brain. Specifically, you’re looking at a cross-section of a mouse hippocampus that’s packed with dentate granule neurons and their signal-transmitting arms, called axons, (light green). Note how the axons’ short, finger-like projections, called filopodia (bright green), are interacting with a neuron (red) to form a “memory trace” network. Functioning much like an online search engine, memory traces use bits of incoming information, like the first few notes of a song, to locate and pull up more detailed information, like the complete song, from the brain’s repository of memories in the cerebral cortex.


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Everybody knows that it’s important to stay alert behind the wheel or while out walking on the bike path. But our ability to react appropriately to sudden dangers is influenced by whether we feel momentarily tired, distracted, or anxious. How is it that the brain can transition through such different states of consciousness while performing the same routine task, even as its basic structure and internal wiring remain unchanged?

A team of NIH-funded researchers may have found an important clue in zebrafish, a popular organism for studying how the brain works. Using a powerful new method that allowed them to find and track brain circuits tied to alertness, the researchers discovered that this mental state doesn’t work like an on/off switch. Rather, alertness involves several distinct brain circuits working together to bring the brain to attention. As shown in the video above that was taken at cellular resolution, different types of neurons (green) secrete different kinds of chemical messengers across the zebrafish brain to affect the transition to alertness. The messengers shown are: serotonin (red), acetylcholine (blue-green), and dopamine and norepinephrine (yellow).

What’s also fascinating is the researchers found that many of the same neuronal cell types and brain circuits are essential to alertness in zebrafish and mice, despite the two organisms being only distantly related. That suggests these circuits are conserved through evolution as an early fight-or-flight survival behavior essential to life, and they are therefore likely to be important for controlling alertness in people too. If correct, it would tell us where to look in the brain to learn about alertness not only while doing routine stuff but possibly for understanding dysfunctional brain states, ranging from depression to post-traumatic stress disorder (PTSD).


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