Left Right Brain Signals

New tool shows what happens when we learn

Researchers at Scripps Research have developed a novel tool to monitor brain plasticity.

Researchers from Scripps Research looked at how the levels of various proteins in brain cells change in response to brain activity.

Scientists at the Scripps Research Institute have developed a new tool to monitor brain plasticity – the process by which our brains remodel and physically adapt as we learn and experience new things, such as For example, watching a movie or learning a new song or language. Her method, which studies the proteins produced by different brain cell types, has the potential to provide fundamental explanations for how the brain works and provide insight into the many brain disorders in which plasticity is disrupted.

Previous research, carried out in a number of laboratories, has shown how brain activity triggers changes in gene expression in neurons, an early step in plasticity. The team’s research, recently published in the Journal of Neurosciencefocuses on the next important level of plasticity – the conversion of the genetic code into proteins.

“We still don’t understand all of the mechanisms underlying how cells in our brain change in response to experience, but this approach gives us a new window into the process,” says Hollis Cline, Ph.D., Hahn professor and Chair of Neuroscience at Scripps Research and senior author of the new work.

Two things happen when you learn something new. First, neurons in your brain immediately relay electrical signals along new neural pathways. This eventually leads to changes in the physical structure of the brain cells and their connections. However, scientists have long wondered what happens between these two steps. Ultimately, how does the brain experience more substantial changes as a result of this electrical activity in neurons? Also, how and why does this plasticity deteriorate with age and certain diseases?

Previously, researchers have studied how genes in neurons turn on and off in response to brain activity, hoping to gain insight into plasticity. With the advent of high-throughput gene sequencing technologies, tracking genes in this way has become relatively easy. But most of these genes encode proteins — the actual workhorses of cells, the levels of which are harder to monitor. But Cline, working closely with Scripps Professor John Yates III, Ph.D., and Associate Professor Anton Maximov, Ph.D., wanted to study directly how proteins change in the brain.

“We wanted to jump in the deep end of the pool and see which proteins are important for brain plasticity,” says Cline.

The team designed a system into which they could introduce a specially labeled amino

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Any substance which, when dissolved in water, gives a pH of less than 7.0 or donates a hydrogen ion.

” data-gt-translate-attributes=”[{” attribute=””>acid—one of the building blocks of proteins—into one type of neuron at a time. As the cells produced new proteins, they would incorporate this amino acid, azidonorleucine, into their structures. By tracking which proteins contained the azidonorleucine over time, the researchers could monitor newly made proteins and distinguish them from pre-existing proteins.

Cline’s group used the azidonorleucine to track which proteins were made after mice experienced a large and widespread spike in brain activity, mimicking what happens at a smaller scale when we experience the world around us. The team focused on cortical glutamatergic neurons, a major class of brain cells responsible for processing sensory information.

After the increase in neural activity, the researchers discovered levels of 300 different proteins changed in the neurons. While two-thirds increased during the spike in brain activity, the synthesis of the remaining third decreased. By analyzing the roles of these so-called “candidate plasticity proteins”, Cline and her colleagues were able to gain general insight into how they might impact plasticity. Many of the proteins are related to the structure and shape of neurons, for instance, as well as how they communicate with other cells. These proteins suggested ways in which brain activity can immediately begin to impact connections between cells.

Additionally, a number of the proteins were related to how

The study was funded by the National Institutes of Health, the Hahn Family Foundation, and the Harold L. Dorris Neurosciences Center Endowment Fund.


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