Salk Researchers Study Neuroscience Behind Finding Lost Items
March 21, 2013

Salk Researchers Study Neuroscience Behind Finding Lost Items

Alan McStravick for — Your Universe Online

As if it wasn´t enough that Jonas Salk was responsible for the eradication of polio, now the institute named for him is tackling an even more universally deleterious condition: understanding the neural processes behind helping you to locate lost items.

Though the results of the study have been adapted to the common human experience of finding one´s misplaced keys or automobile or cell phone, the research involved observing mouse subjects and monitoring the activity of individual neurons at different time points.

The area of the brain researchers focused on was the hippocampus. The hippocampus is a region within the brain known to be responsible for storing and retrieving memories of different environments.

The scientists at the Salk Institute for Biological Studies claim their study explains how the brain is able to keep track of the incredibly rich and complex environments we are exposed to on a daily basis. One discovery, in particular, showed the dentate gyrus, a subregion of the hippocampus, actually helps to keep memories of similar events and environments separate. Their study was recently published in the journal eLife. The research team believes their findings could have far-reaching applications, helping to identify how neurodegenerative diseases, such as Alzheimer´s disease, effectively strip people of these abilities.

"Every day, we have to remember subtle differences between how things are today, versus how they were yesterday - from where we parked our car to where we left our cellphone," says Fred H. Gage, senior author on the paper and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease at Salk. "We found how the brain makes these distinctions, by storing separate 'recordings' of each environment in the dentate gyrus."

The distinction made by the brain mentioned above, is known as pattern separation. This process involves the brain recognizing a complex memory and then converting it into a representation that is less easily confused with other similar memories. According to the team, there are computational models of brain function that suggest the dentate gyrus is key to the process of pattern separation of memories. It does this by activating different groups of neurons when an animal is in different environments.

Previous studies of the dentate gyrus presented findings at odds with theoretical predictions on its behavior. These studies showed the same populations of neurons were active in different environments, but that the ability to distinguish new surroundings was affected by the changing rate of electrical impulses sent by the neurons. This discrepancy had, until now, vexed neuroscientists and obscured our understanding of memory formation and retrieval.

The Salk team, in an effort to solve this neurological mystery, compared the functioning of the mouse dentate gyrus and another region of the hippocampus, known as CA1.

The method employed by the team involved removing mice from their original familiar chamber and placing them into a new, novel chamber. This was done so the mice would have to learn about a new environment. During this process, the researchers recorded which hippocampal neurons were active while the mice learned their new surroundings.

Once this process was complete, the mice were divided into two groups. The first group was returned to the novel chamber while the second group was introduced to a slightly modified chamber. Those in the first group underwent a measurement of memory recall. The second group of mice was observed to measure discrimination of a new environment.

During this time of the study, the active neurons were labeled in order to determine if the neural activity noted in the initial introduction to the novel chamber was identical to the neural activity necessary for both recall and discrimination of small differences between environments.

In fact, the team, upon comparing the two measures of neural activity, found the dentate gyrus and CA1 sub-regions functioned differently. In CA1, the same neurons that were active during the initial learning episode were also active when the mice retrieved memories. However, in the dentate gyrus, distinct groups of cells were active during the learning episodes and retrieval. The team also learned that by exposing the mice to two subtly different environments, the dentate gyrus experienced the activation of two distinct groups of cells.

"This finding supported the predictions of theoretical models that different groups of cells are activated during exposure to similar, but distinct, environments," says Wei Deng, a Salk postdoctoral researcher and first author on the paper. "This contrasts with the findings of previous laboratory studies, possibly because they looked at different sub-populations of neurons in the dentate gyrus."

These findings are important in understanding the formation and storage of memory. The team states the act of recalling a memory does not always involve reactivation of the same neurons responsible for the initial encoding of the memory. Additionally, the findings support the idea that the dentate gyrus performs pattern separation by using distinct populations of cells to represent similar but non-identical memories.

Also contributing to this study was Mark Mayford of the Scripps Research Institute. Funding support was provided by the James S. McDonnell Foundation, the Lookout Fund, the Kavli Institute for Brain and Mind and the National Institutes of Health.

The import of this study is that the findings will help to clarify the mechanisms at work in memory formation. By understanding these processes, future research can be conducted helping to shed light on the systems that are disrupted by injuries and diseases of the nervous system.