In a study, due to appear in the March 30 issue of Cell, researchers at MIT’s Picower Institute for Learning and Memory have discovered, for the first time, that neurons at different stages of their life cycles potentially perform two separate functions, such as forming distinct memories of almost identical situations, and the ability to recall an entire event when prompted by a tiny detail.
The study describes a brain structure that produces new neurons in adults as a possible vital target for developing drugs for the treatment of memory disorders.
Lead author, Toshiaki Nakashiba at the Picower Institute said that an imbalance between young and old neurons in the brain region, called dentate gyrus can potentially disrupt memory formation, recalling and potentially affect cognitive dysfunctions related to post-traumatic stress disorder (PTSD), as well as aging. In dentate gyrus, only one of the two brain sites continuously generates new neurons throughout adult life.
Co-author Susumu Tonegawa, Picower Professor of Neuroscience at the Picower Institute explained:
“In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging.”
The brain detects small differences between similar experiences by pattern separation. Humans are able to recall explicit content of earlier memories with only limited clues related to the original experience when these patterns are complete. For instance, a person who has dinner at the same French restaurant two nights in a row makes similar experiences or observations on both occasions, like the menu, the surroundings, the time of their visit, etc.
The distinct memories that the person’s brains forms for each event are called pattern separation. If a friend, for instance, mentions a liking for onion soup some time later, the person may recall not only the dish they had at the restaurant, but the entire experience of which people were at the restaurant, what they did after the meal, etc. This process is recalled by pattern completion.
Whilst pattern separation forms a unique new memory based on differences between experiences, pattern completion recalls memories by identifying similarities. People who have suffered severe brain injury or trauma are often unable to recognize their family and friends’ faces that they see on a regular basis, whilst others with PTSD are unable to forget harrowing events.
Tonegawa explains:
“Impaired pattern separation due to loss of young neurons may shift the balance in favor of pattern completion, which may underlie recurrent traumatic memory recall observed in PTSD patients.”
For a long time, neuroscientists believed that these two opposing and competing processes occur in different neural circuits within the hippocampus, thinking that the dentate gyrus, a structure of significant interest for its plasticity within the nervous system and its impact on conditions ranging from depression and epilepsy to traumatic brain injury, is involved in pattern separation, whilst the CA3 region is involved in pattern completion. However, the MIT researchers discovered that the neurons spawned by the dentate gyrus alone could potentially have distinct roles as they age.
The MIT researchers explored a pattern separation in mice that learned to distinguish between two chambers, of which one was safe and the other gave them an unpleasant shock to their feet. To assess the mice pattern completion abilities, the researchers gave the mice limited cues in finding their way out of a maze they knew how to negotiate earlier. They compared normal mice with mice that lacked young or old neurons, and discovered that the mice exhibited defects in pattern completion or separation, depending on which set of neurons was depleted. Previous research supported the idea that the dentate gyrus or young neurons performed pattern separation when examining pattern separation, by manipulating the entire dentate gyrus or only adult-born young neurons.
Nakashiba concluded:
“By studying mice genetically modified to block neuronal communication from old neurons–or by wiping out their adult-born young neurons–we found that old neurons were dispensable for pattern separation, whereas young neurons were required for it. Our data also demonstrated that mice devoid of old neurons were defective in pattern completion, suggesting that the balance between pattern separation and completion may be altered as a result of loss of old neurons.”
Written by Petra Rattue