New mechanism as to how the brain links events from memory discovered

New mechanism as to how the brain links events from memory discovered

“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 Mohsin Ahmed, clinical psychiatrist, is a powerful example of the brain’s powerful ability to remember and connect events separated in time. This new study published by scientists at Columbia’s Zuckerman Institute has shed light on how the brain can form such enduring links. The hippocampus, a brain region critical for memory, 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. The prevailing view has been that cells in the hippocampus keep up a level of persistent activity to associate such events and turning these cells off would thus disrupt learning.

hippocampus

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. They recorded the activity of thousands of neurons in the animals’ hippocampus simultaneously over the course of each trial for many days.

To make sense of the information they collected, the researchers teamed up with computational neuroscientists who develop powerful mathematical tools to analyze vast amounts of experimental data. They expected to see repetitive, continuous neural activity that persisted during the fifteen-second gap, an indication of the hippocampus at work linking the auditory tone and the air puff but when they began to analyze the data, no such activity was seen. Instead, the neural activity recorded during the fifteen-second time gap was sparse. Only a small number of neurons fired, and they did so seemingly at random. This sporadic activity looked distinctly different from the continuous activity that the brain displays during other learning and memory tasks.

2-photon calcium imaging (5x speed) of the activity responses of neurons in hippocampal area CA1 of a mouse as it learns to associate a neutral tone (conditioned stimulus) with airpuffs (unconditioned stimulus) across a 15 second time delay (Credit: Mohsin Ahmed/Losonczy lab/Columbia’s Zuckerman Institute).

To understand the activity, they had to shift the way they analyzed data and use tools designed to make sense of random processes. Ultimately, the researchers discovered a pattern in the randomness: a style of mental computing that seems to be a remarkably efficient way that neurons store information. Instead of communicating with each other constantly, the neurons save energy – perhaps by encoding information in the connections between cells, called synapses, rather than through the electrical activity of the cells.

This newly discovered mechanism of the hippocampus may 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.

“While our study does not explicitly model the clinical syndromes of either of these disorders, it can be immensely informative. For example, it can help us to model some aspects of what may be happening in the brain when patients experience a fearful association between two events that would, to someone else, not elicit fright or panic.”

says Dr. Ahmed, who is also a member of the Losonczy lab at Columbia’s Zuckerman Institute.

References:

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