Creative Minds: Seeing Memories in a New Light

Posted on November 28th, 2017 by Dr. Francis Collins

Whether it’s lacing up for a morning run, eating blueberry scones, or cheering on the New England Patriots, Steve Ramirez loves life and just about everything in it. As an undergraduate at Boston University, this joie de vivre actually made Ramirez anxious about choosing just one major. A serendipitous conversation helped him realize that all of the amazing man-made stuff in our world has a common source: the human brain.

So, Ramirez decided to pursue neuroscience and began exploring the nature of memory. Employing optogenetics (using light to control brain cells) in mice, he tagged specific neurons that housed fear-inducing memories, making the neurons light sensitive and amenable to being switched on at will.

In groundbreaking studies that earned him a spot in Forbes 2015 “30 Under 30” list, Ramirez showed that it’s possible to reactivate memories experimentally in a new context, recasting them in either a more negative or positive behavior-changing light [1–3]. Now, with support from a 2016 NIH Director’s Early Independence Award, Ramirez, who runs his own lab at Boston University, will explore whether activating good memories holds promise for alleviating chronic stress and psychiatric disease.

Memories might seem as though they are stored as static records in the brain, much like books in a bookcase. But they really aren’t. When a memory is recalled, the brain will actively process it, adding or subtracting features. This allows recollections from as far back as childhood to evolve as long as we care to remember them. A practical consequence is that the only memories we should really trust to be completely accurate are the ones we’ve never recalled.

Using his mouse system, Ramirez plans to examine the effects of this “living” memory on behaviors, including those related to anxiety and avoidance of once-enjoyable activities. He wants to learn whether sustained activation of a good memory before an animal experiences stress can afford them some protection.

Much of this work will occur in the hippocampus, a region of the brain involved in the memory of facts and events. Ramirez and his colleagues will also study how the hippocampus routes its signals to other parts of the brain, such as the amygdala, which responds to fear and stress; and the cerebral cortex, the center of human cognition.

By tracking memory circuits throughout the brain, Ramirez hopes to see where and how to change such signals and modify behaviors. As he learns more about the way the brain works in the mouse, it may help to map out better strategies for treating or perhaps even preventing depression, post-traumatic stress disorder, and other conditions in humans.

The goal isn’t to eliminate the memory of difficult experiences, but to make it possible to reflect on them in a more positive light. That’s something Ramirez knows a lot about. His parents immigrated to the United States from El Salvador, and his life growing up here wasn’t always easy. But, Ramirez says those experiences keep him grounded. No matter how tough things seem, he knows how lucky he’s been. That’s why he continues to love life and its many possibilities.

References:

 [1] Optogenetic stimulation of a hippocampal engram activates fear memory recall. Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, Tonegawa S. Nature. 2012 Mar 22;484(7394):381-385.

[2] Creating a false memory in the hippocampus. Ramirez S, Liu X, Lin PA, Suh J, Pignatelli M, Redondo RL, Ryan TJ, Tonegawa S. Science. 2013 Jul 26;341(6144):387-391.

[3] Activating positive memory engrams suppresses depression-like behaviour. Ramirez S, Liu X, MacDonald CJ, Moffa A, Zhou J, Redondo RL, Tonegawa S. Nature. 2015 Jun 18;522(7556):335-339.

Links:

Ramirez Lab (Boston University, Boston)

Steve Ramirez (Forbes 2015 30 Under 30)

Ramirez NIH Project Information (NIH RePORTER)

NIH Director’s Early Independence Award (Common Fund)

NIH Support: Common Fund