Scientists Change the Brain to Make New Memories

By studying how memories are made, UC Irvine neurobiologists created new, specific memories by direct manipulation of the brain, which could prove key to understanding and potentially resolving learning and memory disorders.

Research led by senior author Norman M. Weinberger, a research professor of neurobiology & behavior at UC Irvine, and colleagues has shown that specific memories can be made by directly altering brain cells in the cerebral cortex, which produces the predicted specific memory. The researchers say this is the first evidence that memories can be created by direct cortical manipulation.
 
Suppose you heard the sound of skidding tires, followed by a car crash. The next time you heard such a skid, you might cringe in fear, expecting a crash to follow -- suggesting that somehow, your brain had linked those two memories so that a fairly innocuous sound provokes dread.

MIT neuroscientists have now discovered how two neural circuits in the brain work together to control the formation of such time-linked memories. This is a critical ability that helps the brain to determine when it needs to take action to defend against a potential threat, says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the Jan. 23 issue of Science.
 
"It's important for us to be able to associate things that happen with some temporal gap," says Tonegawa, who is a member of MIT's Picower Institute for Learning and Memory. "For animals it is very useful to know what events they should associate, and what not to associate."
The interaction of these two circuits allows the brain to maintain a balance between becoming too easily paralyzed with fear and being too careless, which could result in being caught off guard by a predator or other threat.
The paper's lead authors are Picower Institute postdocs Takashi Kitamura and Michele Pignatelli.
 
Linking memories
Memories of events, known as episodic memories, always contain three elements -- what, where, and when. Those memories are created in a brain structure called the hippocampus, which must coordinate each of these three elements.
To form episodic memories, the hippocampus also communicates with the region of the cerebral cortex just outside the hippocampus, known as the entorhinal cortex. The entorhinal cortex, which has several layers, receives sensory information, such as sights and sounds, from sensory processing areas of the brain and sends the information on to the hippocampus.
 
Study results appeared in the August 29 issue of Neuroscience.
During the research, Weinberger and colleagues played a specific tone to test rodents then stimulated the nucleus basalis deep within their brains, releasing acetylcholine (ACh), a chemical involved in memory formation. This procedure increased the number of brain cells responding to the specific tone. The following day, the scientists played many sounds to the animals and found that their respiration spiked when they recognized the particular tone, showing that specific memory content was created by brain changes directly induced during the experiment. Created memories have the same features as natural memories including long-term retention.
 
"Disorders of learning and memory are a major issue facing many people and since we've found not only a way that the brain makes memories, but how to create new memories with specific content, our hope is that our research will pave the way to prevent or resolve this global issue," said Weinberger, who is also a fellow with the Center for the Neurobiology of Learning & Memory and the Center for Hearing Research at UC Irvine.
 
The creation of new memories by directly changing the cortex is the culmination of several years of research in Weinberger's lab implicating the nucleus basalis and ACh in brain plasticity and specific memory formation. Previously, the authors had also shown that the strength of memory is controlled by the number of cells in the auditory cortex that process a sound.