What exactly is a memory, according to neuroscience?
Sheffield: We’re still working on that as a field. There are approximately 100 billion neurons in the human brain. They talk to each other by forming connections with each other called synapses. And the total number of synapses in the brain is around 100 trillion.
The brain is extremely complex, and information is flowing throughout all those connections in very complex ways. In neuroscience, we are trying to understand how that works and how it gives rise to everything that brains can do: all your thoughts, memories, feelings. And we do that by looking at what the brain is doing, in terms of patterns of activity and the connections between neurons.
Where are memories located in the brain?
Sheffield: Other labs have studied what they call memory engrams, a proposed physical substrate of a memory that exists somewhere in the brain. They tagged the neurons that were active during the memory formation phase. Those neurons were in the hippocampus part of the brain.
This gives rise to the idea that you’ve got thousands, if not millions of memories of your past experiences, and they’re encoded by specific subpopulations of neurons that are all connected to each other in complex ways.
Ramirez-Matias: We think of memories that are active during some experience and then re-activated when a memory is retrieved. Some of those neurons care more about particular features of those experiences, like the context that it happened in, or the physical space where it occurred. Others care more about emotion, and when we think about past experiences, emotionally salient ones are typically more memorable.
How does the brain retrieve memories?
Sheffield: There’s a process in the hippocampus called pattern completion, and this is part of how we think memories are retrieved. When you are in an environment, there’s something that we call a cue—maybe it’s a visual cue—that might remind you of something. The cue allows you to retrieve a memory. And it does that, if it works correctly.
But you can have a single cue that triggers the hippocampus to then complete the pattern of activity that retrieves the full memory. We call that pattern completion. The wiring in the circuitry that exists there allows for that process to happen. Sometimes, when you trigger the system, you’re not providing enough information to the hippocampus for it to be able to complete that pattern and retrieve that memory.
That’s why sometimes you can remember and then other times you can’t.
Why is emotion important in memories?
Sheffield: One of the things we’re really interested in is how emotion modulates memories. How does the neural activity and the connections between them allow for memories to form and for them to be consolidated and retrieved at some later time? And how do emotion and the circuits related to emotion modulate that process?
Dopamine has been associated with reward and positive feelings. There are projections from an area of the brain called the ventral tegmental area. That’s where a lot of the dopamine neurons exist, and they project all over the brain. They signal to the brain that this is a really positive experience, so let’s release some dopamine. And that’s going to modulate how the brain works.
How does your lab study memory formation?
Sheffield: One of the more interesting ways we approach this question is we have mice run around in a virtual reality environment, and we have a reward at the end of a maze. When they are done, we can “teleport” them back to the start of the maze, so that they have to approach the reward again.
What is cool about our lab is that we have this really high-resolution imaging of neuronal activity, so we can see single neurons light up as the mice run the maze. The technique we use allows us to look at 1,000, 2,000, maybe 3,000 neurons at any particular moment. We can see those neurons with our microscope, and we can see their activity. It’s like a firework display. We’re trying to ask: W, what does that population and those dynamics tell us? Can we relate that to what the animal is doing?