Researchers tickled mice whiskers and peered into their brains so precisely they were able to see how proteins clustered on nerve cells as memories formed.
The technique could be broadly useful for future studies not only on memory and learning but also on what goes wrong in disorders like autism, Alzheimer’s disease, and schizophrenia.
“As far as we know, no one has ever been able to look at receptor proteins in live animals before,” says Richard Huganir, director of neuroscience at Johns Hopkins University School of Medicine.
“This allows us to get a more accurate picture of what’s really happening as the brain processes experiences into memories.”
At the heart of the story are AMPA receptors, proteins that live on the outside of nerve cells. They receive signals in the form of AMPA molecules and play an important role in strengthening and weakening synapses, the connections between nerve cells that form memories.
Until now, scientists were limited to studying AMPA receptors in nerve cells grown in the laboratory or in tissue samples; neither of those fully reflects the complex circuitry, hormones, and neurochemicals of a living brain.
For the new study, published in Nature Neuroscience, researchers created mice with AMPA receptors that glow under light from a special microscope. The microscope can focus at a depth of 0.5 millimeters, seeing into the outer layer of the brain, called the cortex.
There, thousands of nerve cells carry information from every part of the body; each mouse whisker has a group of dedicated nerve cells there called barrel fields.
Deeper into the brain
The team imaged each mouse immediately before and after tickling a single whisker for an hour. What they saw surprised them: tickling alone was sufficient to increase the number of AMPA receptors in and strengthen the synapses of the barrel fields for the tickled whiskers.
Checking back over the next few days, the researchers found that the AMPA receptor levels remained high, suggesting that the whisker-tickling experience had a long-term effect on the mice’s memories.
“The mysteries are the purpose that is served by strengthening these synapses, and whether more AMPA receptors are being made or if they are moving in from somewhere else,” says postdoctoral fellow Yong Zhang. “Future studies will address those questions.”
“This technique opens up many more possibilities, like visualizing learning at the molecular level as it is happening in the intact brain in healthy mice and in mouse models of brain disorders.”
The group first plans to apply the new technique to see what happens as mice learn a complex motor task. With better optics, they also hope to one day be able to go deeper into the brain to areas like the hippocampus, which has a crucial role in memory formation and has been implicated in neurological disorders like autism, Alzheimer’s disease, and schizophrenia.
The National Institute of Mental Health and the Howard Hughes Medical Institute funded the study.
Source: Johns Hopkins University