Memory linked to specific brain cells

Happy or frightful memories like the first kiss or a bump in the night leave memory traces or engrams that we may stimulate when we remember things in the past, complete with time, place and all the sensations we experienced. The online journal Nature reveals the answer to the question of whether these engrams are conceptual or whether they consist of a physical network of neurons within the brain. Researchers at MIT decided to demonstrate that memories do, in fact, reside in specific brain cells and that by merely activating a tiny fraction of these cells a person can call an entire memory event. This would explain, for instance, how Marcel Proust was able to recall childhood memories from the smell of a Madeleine cookie he loved as a child. Leading researcher Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT says: "We demonstrate that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells, in this case by light. This is the rigorously designed 21st-century test of Canadian neurosurgeon Wilder Penfield's early-1900s accidental observation suggesting that mind is based on matter." ? Penfield's epilepsy treatment consisted of scooping out parts of the patients' brains where the seizures originated. He then stimulated the brain with tiny jolts of electricity in order to ensure that only the problematic neurons were destroyed, whilst the locally anesthetized patients reported during the procedure what they had experienced. When Penfield stimulated just a few neurons in the hippocampus, which is now known to be involved with forming and recalling episodic memories, he was astonished to find that some patients vividly recalled entire comprehensive events. Since then, this has been the cause of continued investigations. However, until now, researchers have been unable to provide evidence that, in order to cause memory recall, it is sufficient to simply reactivate the hippocampus directly. Seven years ago scientists discovered a new technology called optogenetics that is able to stimulate genetically modified neurons so it expresses light-activated proteins. Co-author Xu Liu, a postdoc in Tonegawa's lab says: "We thought we could use this new technology to directly test the hypothesis about memory encoding and storage in a mimicry experiment." Steve Ramirez, another co-author and a graduate student in Tonegawa's lab adds: "We wanted to artificially activate a memory without the usual required sensory experience, which provides experimental evidence that even ephemeral phenomena, such as personal memories, reside in the physical machinery of the brain." The first step of their experiment involved identifying a specific set of brain cells within the hippocampus that was only active when a mouse was exploring a new environment. Once they established which genes were activated in the brain cells, they coupled them with the gene for channelrhodopsin-2 (ChR2), which is a light-activated protein used in optogenetics. They then implanted the coupled gene into the mice's dentate gyrus, a part within the hippocampus thought to contribute to the formation of new memories, so they could study the mice by using tiny optical fibers to deliver pulses of light to the neurons. They found an ingenious way to label the physical network of neurons linked to a specific memory engram for a particular experience by ensuring that the light-activated protein would only be expressed in the neurons involved in experiential learning. The mice were then allowed to enter a new environment and received a small shock to the foot after a few minutes of exploration, which taught them to fear the particular environment in which they experienced the shock. The researchers then tagged the brain cells with ChR2, which were activated during the moment the mice experienced fear and observed that these neurons involved in the fear memory were switched on when the mice were later exposed to triggering pulses of light in a completely different environment, and that the mice quickly adopted a defensive, immobile crouch. ?? The result of this light-induced freezing indicates that the animals indeed recalled the memory of being shocked and perceived a replay of a fearful memory, even though the memory was artificially reactivated. Liu comments: "Our results show that memories really do reside in very specific brain cells and simply by reactivating these cells by physical means, such as light, an entire memory can be recalled." ?? Tonegawa refers to the 17th-century French philosopher who wrote, "I think, therefore I am," saying: "René Descartes didn't believe the mind can be studied as a natural science. He was wrong. This experimental method is the ultimate way of demonstrating that mind, like memory recall, is based on changes in matter." The approach could also potentially be used when studying neurodegenerative and neuropsychiatric disorders. Ramirez says: "The more we know about the moving pieces that make up our brains the better equipped we are to figure out what happens when brain pieces break down."