A cross-section of a rat’s brain, showing where the key decisions are made about which is a new memory being made and which is old and familiar (credit: Johns Hopkins University)
Know that feeling when you see someone and realize you may know them (or not)? Now we know actually where in the brain that happens — the CA3 region of the hippocampus, the seat of memory, thanks to Johns Hopkins University neuroscientists.
“You see a familiar face and say to yourself, ‘I think I’ve seen that face.’ But is this someone I met five years ago, maybe with thinner hair or different glasses — or is it someone else entirely?” said James J. Knierim, a professor of neuroscience at the university’s Zanvyl Krieger Mind/Brain Institute who led the research, described in the current issue of the journal Neuron.
Is that you under that beard? Oops, excuse me. “That’s one of the biggest problems our memory system has to solve, Kneirim said. “The final job of the CA3 region is to make the decision: Is it the same or is it different? Usually you are correct in remembering that this person is a slightly different version of the person you met years ago.
“But when you are wrong, and it embarrassingly turns out that this is a complete stranger, you want to create a memory of this new person that is absolutely distinct from the memory of your familiar friend, so you don’t make the mistake again.”
Would you like chocolate sprinkles on that cheese? Knierim and associates implanted electrodes in the hippocampus of rats and monitored them as they got to know an environment and as that environment changed. They trained the rats to run around a track, eating chocolate sprinkles. The track floor had four different textures — sandpaper, carpet padding, duct tape and a rubber mat.
The rat could see, feel and smell the differences in the textures. Meanwhile, a black curtain surrounding the track had various objects attached to it. Over 10 days, the rats built mental maps of that environment.
Messing with rat minds for fun and science. Then the experimenters changed things up. They rotated the track counter-clockwise, while rotating the curtain clockwise, creating a perceptual mismatch in the rats’ minds. The effect was similar, Knierim said, to if you opened the door of your home and all of your pictures were hanging on different walls and your furniture had been moved.
“Would you recognize it as your home or think you are lost?” he said. “It’s a very disorienting experience and a very uncomfortable feeling.”
Even when the perceptual mismatch between the track and curtain was small, the “pattern-separating” part of CA3 almost completely changed its activity patterns, creating a new memory of the altered environment. But the “pattern-completing” part of CA3 tended to retrieve a similar activity pattern used to encode the original memory, even when the perceptual mismatch increased.
The findings, which validate models about how memory works, could help explain what goes wrong with memory in diseases like Alzheimer’s and could help to preserve people’s memories as they age.
This research was supported by the National Institutes of Health grants and by the Johns Hopkins University Brain Sciences Institute.
Abstract of Neural population evidence of functional heterogeneity along the CA3 transverse axis: Pattern completion vs. pattern separation
Classical theories of associative memory model CA3 as a homogeneous attractor network because of its strong recurrent circuitry. However, anatomical gradients suggest a functional diversity along the CA3 transverse axis. We examined the neural population coherence along this axis, when the local and global spatial reference frames were put in conflict with each other. Proximal CA3 (near the dentate gyrus), where the recurrent collaterals are the weakest, showed degraded representations, similar to the pattern separation shown by the dentate gyrus. Distal CA3 (near CA2), where the recurrent collaterals are the strongest, maintained coherent representations in the conflict situation, resembling the classic attractor network system. CA2 also maintained coherent representations. This dissociation between proximal and distal CA3 provides strong evidence that the recurrent collateral system underlies the associative network functions of CA3, with a separate role of proximal CA3 in pattern separation.