Assoc. Prof. Mark Sheffield at the entrance of the UChicago Neuroscience Institute.
Photo by Stephen L. Garrett
Within that, their work focuses on “place cells,” which are neurons in the hippocampus that activate only when an animal is in a certain part of its given territory. Scientists refer to that physical area as a corresponding “place field.”
According to this concept, different neurons have their place fields at different locations, working together to cover the whole environment and form what’s known as a cognitive map—an internal representation of the outside world. The discovery of this phenomena was awarded the 2014 Nobel Prize in Medicine.
Better understanding the mechanics could be key to one day treating disorders related to memory, such as Alzheimer’s disease and schizophrenia.
The new UChicago study outlines the ways in which connections between neurons—called synapses—strengthen or weaken in response to events and the activity they cause in the brain. These changes are called synaptic plasticity. While neuroscientists believe they play an important role in storing memories, the rules governing the process are not well understood.
To learn more, postdoctoral researcher Antoine Madar studied place cell activity recorded in the brains of mice as they scampered through different environments.
“We know a lot about the physiology that supports synaptic plasticity, but we usually don't know how important those things are for learning,” Madar said.
In the study, the mice first ran through a familiar environment, then switched to an unfamiliar one. The researchers expected to see the same patterns of activity when the mice were in a place they knew, and different patterns as they learned a new environment. Instead, they saw the activity was different every time.
Some changes in place cell activity were subtle, with the cell firing in a slightly different location than the previous time. Others were more drastic, jumping to a completely different location.
“These changes in representation, during learning and after, must be driven by synaptic plasticity—but what kind of plasticity exactly? It’s hard to know, because we don’t have the technology to measure that directly in behaving animals,” Sheffield said.
To understand what drives the constant shifts, Madar built a computational model of hippocampal neurons and tested different plasticity rules to see which best matched the mouse data.
The traditional view is that the more two neurons fire together, the stronger their connection becomes—when they fire separately, their connection weakens.
But the new research suggests a newer model, known as Behavioral Timescale Synaptic Plasticity, better explained how brain activity continually reshapes the way memories are recorded. Because this model was only recently discovered, comparing the rule to their data revealed new insights about the chemical processes involved.
Though the research shows that hippocampal activity is much more dynamic during memory formation than previously thought, it’s still not clear what purpose these shifting representations could serve.
Sheffield offered a possible explanation.
“One idea is that these dynamics in memory representations are encoding slight changes in the experience,” Sheffield said. “These subtle differences in setting, odors, time—all these slight changes in experience could be encoded into the memory through the changes in these place fields. They're not just encoding the environment, they’re encoding the entire experience that occurs there.”
