Mice study sheds light on how the brain links events to form a memory

Mice study sheds light on how the brain links events to form a memory

A woman walking down the street hears a bang. Several moments later she discovers her boyfriend, who had been walking ahead of her, has been shot. A month later, the woman checks into the emergency room. The noises made by garbage trucks, she says, are causing panic attacks. Her brain had formed a deep, lasting connection between loud sounds and the devastating sight she witnessed. This story, relayed by clinical psychiatrist and co-author of a new study Mohsin Ahmed, MD, PhD, is a powerful example of the brain's powerful ability to remember and connect events separated in time. And now, in that new study in mice published today in Neuron , scientists at Columbia's Zuckerman Institute have shed light on how the brain can form such enduring links. The scientists uncovered a surprising mechanism by which the hippocampus, a brain region critical for memory, builds bridges across time: by firing off bursts of activity that seem random, but in fact make up a complex pattern that, over time, help the brain learn associations. By revealing the underlying circuitry behind associative learning, the findings lay the foundation for a better understanding of anxiety and trauma- and stressor-related disorders, such as panic and post-traumatic stress disorders, in which a seemingly neutral event can elicit a negative response. We know that the hippocampus is important in forms of learning that involve linking two events that happen even up to 10 to 30 seconds apart. This ability is a key to survival, but the mechanisms behind it have proven elusive. With today's study in mice, we have mapped the complex calculations the brain undertakes in order to link distinct events that are separated in time." Attila Losonczy, MD, PhD, principal investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and the paper's co-senior author The hippocampus -- a small, seahorse-shaped region buried deep in the brain -- is an important headquarters for learning and memory. Previous experiments in mice showed that disruption to the hippocampus leaves the animals with trouble learning to associate two events separated by tens of seconds. "The prevailing view has been that cells in the hippocampus keep up a level of persistent activity to associate such events," said Dr. Ahmed, an assistant professor of clinical psychiatry at Columbia's Vagelos College of Physicians and Surgeons, and co-first author of today's study. "Turning these cells off would thus disrupt learning." To test this traditional view, the researchers imaged parts of the hippocampus of mice as the animals were exposed to two different stimuli: a neutral sound followed by a small but unpleasant puff of air. A fifteen-second delay separated the two events. The scientists repeated this experiment across several trials. Over time, the mice learned to associate the tone with the soon-to-follow puff of air. Using advanced two-photon microscopy and functional calcium imaging, they recorded the activity of thousands of neurons, a type of brain cell, in the animals' hippocampus simultaneously over the course of each trial for many days. Related Stories



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