Pew Scholar Investigates How Good and Bad Memories Impact Brain Health

Steve Ramirez, Ph.D., is studying artificial memory manipulation as a therapy for neurodegenerative disorders

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Pew Scholar Investigates How Good and Bad Memories Impact Brain Health
 A wave-like web of fluorescent green brain cells, dotted with the occasional red cell, are spread in curvy lines across a dark blue background
The spindly green cells in this image show the formation of a fearful memory in a region of the brain called the dentate gyrus; red cells reveal the neurons active during recall. This image of memory activation was captured in Steve Ramirez’s lab.
Courtesy of Steve Ramirez

The brain is the body’s central command system, overseeing everything from movement to decision-making. Researchers have long studied the biology of this sophisticated organ—and tried to crack the code of what happens when it falls victim to disorder or disease. In recent years, they’ve made widespread breakthroughs, including finding ways to harness the power of memory to alleviate anxiety and depression.

Pew biomedical scholar Steve Ramirez, Ph.D., wants to take memory manipulation a step further. Using cutting-edge approaches, Ramirez’s lab at Boston University is exploring the mechanics of memory in mice—with the hope of learning how to better ward off neurological disorders and degeneration in humans.

This interview has been edited for length and clarity. 

Steve Ramirez, Ph.D., is an assistant professor in the Department of Psychological and Brain Sciences at Boston University.
Courtesy of Steve Ramirez

 

Q: What’s your lab’s research focus?

A: We study the mechanisms of learning and memory. Specifically, we try to locate and understand the activity of the specific cells involved in holding on to a particular memory. One of our overarching missions is to look at the concept of artificial memory manipulation and reconceptualize it as a way of restoring health back to the brain.

Q: Artificial memory manipulation: What’s that?

A: We pinpoint the location in the brain where we think a memory has come and gone. Then we go in and stimulate (or inhibit) the appropriate cells, artificially leveraging the activity of the cells—either to activate or block a particular memory.

Q: How do you even begin such a process?

A: The first step is to image the physical landscape of memory and see if we can extract any principles from that process. It’s kind of like Google Maps, but for memory. We’ve developed tools to look at which brain cells process positive and negative memories in particular in the last few years.

Q: And what have you found?

A: Surprisingly, good and bad memories seem to be located in physically distinct areas of the brain. That’s promising because we now have specific geographical targets to manipulate.

Q: How could artificial memory manipulation be applied to human health and medicine?

A: We hope to view memory as a kind of antidote through which we can activate positive memories as a way of casting a protective net over the brain to stop or slow down degeneration. Or, in a situation where someone has Alzheimer’s disease, we might be able to go in and activate memories once thought to be lost.

With Alzheimer’s and dementia, we can try to strengthen the good memories before degeneration happens, like putting a seatbelt over them so that they’re protected. Or we might use artificial memory manipulation to prevent degeneration by either decreasing the recollection of negative experiences or increasing recall of positive experiences to try to protect the brain from itself.

Q: Are these artificially induced memories much different from real memories?

A: In addition to giving mice artificial memories, we also run experiments where we trigger real memories (for example, we have them undergo an experience). This helps us compare what happens in the brain when we’re activating a memory versus prompting a real one. A cool recent finding was that, when we look at the brain of an animal when it’s recalling a real memory, it looks startlingly similar to when we artificially activate a memory. When our first discovery of artificially activated memories came out, there was a lot of contention because people wondered whether the activated memory was actually a real memory or just looked like one. This finding helps us to resolve that issue.

Q: What else is your lab studying?

A: One of our projects involves imaging the brain’s activity at a three-dimensional level. A memory is a 3D web of activity made up of sights, smells, sounds, emotions, and a time and place that all engage different brain functions. Working on these 3D maps of learning in the brain will help us get closer to what memory actually looks like.

Q: What’s the long-term goal of this work?

A: The idea of viewing memory as an antidote is something that we hope can touch every aspect of neuroscience as a broad application for psychiatric and neurodegenerative disorders. The goal is to have memory manipulation be not necessarily limited to a given disorder or symptom but instead be something that joins aerobic exercise, social enrichment, gratitude journaling, and a good night’s sleep in our cabinet of tools that prevent brain disorder.

Q: Any final thoughts?

A: I view what we’re doing here with artificially manipulating memories and navigating this uncharted landscape of the brain as a guided exploration to try to extract how memory works. Rather than having tunnel vision about how things should work in science, we’re entertaining the world of possibilities related to the brain and memory. Earth had at least 4 billion years to make our brains possible while we scientists have only a lifetime of under 100 years to try to figure out how it works. So, it’s OK that we don’t have it all fully figured out yet.

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