Posted on by Lawrence Tabak, D.D.S., Ph.D.
The NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is revolutionizing our understanding of the human brain. As described in the initiative’s name, the development of innovative imaging technologies will enable researchers to see the brain in new and increasingly dynamic ways. Each year, the initiative celebrates some standout and especially creative examples of such advances in the “Show Us Your BRAINs! Photo & Video Contest. During most of August, I’ll share some of the most eye-catching developments in our blog series, The Amazing Brain.
In this fascinating image, you’re seeing two stored memories, which scientists call engrams, in the hippocampus region of a mouse’s brain. The engrams show the neural intersection of a good memory (green) and a bad memory (pink). You can also see the nuclei of many neurons (blue), including nearby neurons not involved in the memory formation.
This award-winning image was produced by Stephanie Grella in the lab of NIH-supported neuroscientist Steve Ramirez, Boston University, MA. It’s also not the first time that the blog has featured Grella’s technical artistry. Grella, who will soon launch her own lab at Loyola University, Chicago, previously captured what a single memory looks like.
To capture two memories at once, Grella relied on a technology known as optogenetics. This powerful method allows researchers to genetically engineer neurons and selectively activate them in laboratory mice using blue light. In this case, Grella used a harmless virus to label neurons involved in recording a positive experience with a light-sensitive molecule, known as an opsin. Another molecular label was used to make those same cells appear green when activated.
After any new memory is formed, there’s a period of up to about 24 hours during which the memory is malleable. Then, the memory tends to stabilize. But with each retrieval, the memory can be modified as it restabilizes, a process known as memory reconsolidation.
Grella and team decided to try to use memory reconsolidation to their advantage to neutralize an existing fear. To do this, they placed their mice in an environment that had previously startled them. When a mouse was retrieving a fearful memory (pink), the researchers activated with light associated with the positive memory (green), which for these particular mice consisted of positive interactions with other mice. The aim was to override or disrupt the fearful memory.
As shown by the green all throughout the image, the experiment worked. While the mice still showed some traces of the fearful memory (pink), Grella explained that the specific cells that were the focus of her study shifted to the positive memory (green).
What’s perhaps even more telling is that the evidence suggests the mice didn’t just trade one memory for another. Rather, it appears that activating a positive memory actually suppressed or neutralized the animal’s fearful memory. The hope is that this approach might one day inspire methods to help people overcome negative and unwanted memories, such as those that play a role in post-traumatic stress disorder (PTSD) and other mental health issues.
Stephanie Grella (Boston University, MA)
Ramirez Group (Boston University)
Show Us Your BRAINs Photo & Video Contest (BRAIN Initiative)
NIH Support: BRAIN Initiative; Common Fund