By Matt Wood
As animals experience new things, the connections between neurons, called synapses, strengthen or weaken in response to events and the activity they cause in the brain. Neuroscientists believe that synaptic plasticity, as these changes are called, plays an important role in storing memories.
However, the rules governing when and how much synapses change are not well understood. The traditional view is that the more two neurons fire together, the stronger their connection becomes; when they fire separately, their connection weakens.
New research from the University of Chicago on the hippocampus, a brain area essential for memory, suggests that this is not the whole story. Other rules of synaptic plasticity appear to have a bigger effect and better explain how brain activity continually reshapes the way memories are recorded in the brain.
Patterns of activity and their neuronal representations change a lot as an animal becomes more familiar with a new environment or experience. Surprisingly, those patterns keep evolving even once something is learned, albeit more slowly.
“When you go into a room, it’s new at first but it quickly becomes familiar to you every time you come back,” said Mark Sheffield, PhD, Associate Professor of Neurobiology and the Neuroscience Institute at UChicago and senior author of the new study published in Nature Neuroscience. “So, you might expect that neuronal activity representing that room would settle and become stable, but it continues to change.
“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,” he said.
Shifting place cells
The 2014 Nobel Prize in Medicine was awarded for the discovery of “place cells”: neurons in the hippocampus that activate only when an animal is at a certain spot in a room, called the “place field.” Different neurons have their place fields at different locations in the room, covering the entire environment and forming what’s known as a cognitive map.
In the new study, Antoine Madar, PhD, a postdoctoral researcher in Sheffield’s lab, studied place cell activity recorded in the brains of mice as they scampered through different environments. 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 that the activity was slightly different every time, and reasoned that these changes reflected synaptic plasticity.
To understand what drives these constant changes in neuronal representations, Madar built a computational model of hippocampal neurons, and then applied different plasticity rules to see if they would make place cells behave in the same patterns seen in the mouse data. Instead of the traditional “neurons that fire together wire together” rule, known as Hebbian Spike Timing-Dependent Plasticity (STDP), a different, non-Hebbian rule called Behavioral Timescale Synaptic Plasticity (BTSP) best explained the shifting place field dynamics.