At the Medical College of Georgia, researchers managed to selectively erase unique memories in laboratory mice, potentially leading to therapies for phobias, depression, PTSD, and other debilitating conditions potentially caused by memories of traumatic events.
From the press release:
Dr. Tsien [Joe Z. Tsien, brain scientist and co-director of the Brain & Behavior Discovery Institute at the Medical College of Georgia School of Medicine, pictured] had already created a mouse that couldn’t form memories by eliminating the NMDA receptor, which receives messages from other neurons. He then garnered international acclaim by making “Doogie,” a smart mouse in which a subunit of the NMDA receptor is over-expressed. Younger brains have higher amounts of this NR2B subunit which leaves communication channels between brain cells open longer. That is why young people can learn faster than older adults.
This time he was examining downstream cascades of the NMDA receptor to learn more about memory formation. An abundant protein found only in the brain, called αCaMKII, was a logical place to look because it’s a major signaling molecule for the NMDA receptor. He found that when he over-expressed αCaMKII while a memory was being recalled, that single memory was eliminated.
Receptors such as the NMDA receptor are like front doors to cells, providing an opening for signaling molecules such as calcium. Synapses are the point of communication between two cells, and NMDA receptors are on the receiving end of the message. Like people, neurons change with the signals they receive. “Learning changes the way cells connect to each other,” says Dr. Tsien. To form a memory, the NMDA receptor is activated, which results in the insertion of AMPA receptors into those synapses and subsequent strengthening of the synaptic connections among hundreds of thousands of neurons. Scientists believe that αCaMKII plays an important role in the insertion of AMPA receptors into synapses during learning and subsequent strengthening of connections between neurons to create a memory.
Memory has four distinct stages: learning, consolidation, storage and recall. It has been difficult to dissect the molecular mechanisms of these stages because researchers lacked techniques to manipulate proteins quickly. For example, when researchers disable a gene suspected to play a role in the memory process, the deletion typically occurred throughout the entire period so it was impossible to tell which parts of processes were impaired. Previous technology would take several days to switch off a protein, which is the product of a gene.
So Dr. Tsien’s team developed a powerful chemical-genetic method that allows him to use a pharmacologic inhibitor to instantly turn αCaMKII off and on in a mouse that he genetically engineered to over express this signaling molecule. That enabled him to study exactly what happened if he threw off the natural balance during the retrieval stage.
Press release: Memories selectively, safely erased in mice
