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To track brain plasticity—the way our brains change and physically adapt as we learn and experience things, from viewing a movie to learning a new song or language—scientists at Scripps Research have created a new tool. Their method, which examines the proteins produced by various brain cell types, has the potential to provide fundamental explanations for how the brain functions as well as provide insight into the numerous disorders of the brain where plasticity malfunctions.
Previous research conducted in a number of labs has demonstrated how brain activity triggers changes in gene expression in neurons, an early process to plasticity. The team’s research, which was published on September 7 in the Journal of Neuroscience, focuses on the subsequent crucial stage of plasticity—the translation of the genetic information into proteins.
The approach gives the researchers a new window into the process, but they still don’t completely understand all the mechanisms involved in how cells in our brain change in response to experiences.
Two things take place when you learn something new: Initially, neurons in your brain instantly transmit electrical signals along new pathways. This eventually results in modifications to the physical makeup of brain cells and their connections. But scientists have speculated what occurs between these two actions. What causes the brain to transform in a more lasting way as a result of this electrical activity in neurons? Also, how and why does this adaptability deteriorate with aging and specific diseases?
In an effort to gain understanding of plasticity, researchers have previously looked at how genes in neurons switch on and off in response to brain activity. High-throughput gene sequencing technologies have made it relatively simple to track genes in this way. However, the majority of those genes produce proteins, which are the true workhorses of cells and whose amounts are more challenging to track. But the researchers wanted to look directly at how proteins in the brain change
The researchers wanted to get right in and investigate which proteins are key to brain plasticity.
The team created a technique that allowed them to introduce a particularly marked amino acid—one of the components of proteins—to one type of neuron at a time. This amino acid, azidonorleucine, would be incorporated into the structures of the cells as they made new proteins. The researchers were able to monitor freshly produced proteins and distinguish them from existing proteins by monitoring which proteins had the azidonorleucine over time.
The team tracked which proteins were produced following a significant and widespread increase in brain activity in mice, simulating what occurs at a smaller scale when we encounter the environment. The group concentrated on cortical glutamatergic neurons, a significant class of brain cells in charge of processing sensory data.
The researchers found that 300 distinct proteins had their levels altered in the neurons following the rise in brain activity. During the rise in brain activity, two-thirds rose, but the synthesis of the remaining third reduced. The team were able to develop a general understanding of how these so-called “candidate plasticity proteins” might affect plasticity by examining the roles of these proteins. Numerous proteins are involved in the form and function of neurons as well as their intercellular communication. These proteins offered explanations for how brain activity might begin to affect cell connections right away.
A few of the proteins were also related to the way DNA is stored inside of cells; altering this storage can change which genes a cell can access and use over the course of a long time. This raises the possibility that a short increase in brain activity may trigger longer-lasting brain remodeling.
According to the researchers, this is a “clear mechanism” through which changes in brain activity can cause waves of gene expression to last for several days.
By employing this technique, the researchers expect to identify and investigate more possible plasticity proteins, such as those that might alter in various types of brain cells in response to a novel visual stimuli in animals. Through studies of how brain activity affects protein creation in young versus elderly and healthy versus diseased brains, the researchers claim that their technology could also provide insight into brain disorders and aging.
Sources:
Schiapparelli, L. M., Xie, Y., Sharma, P., McClatchy, D. B., Ma, Y., Yates, J. R., 3rd, Maximov, A., & Cline, H. T. (2022). Activity-Induced Cortical Glutamatergic Neuron Nascent Proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience, 42(42), 7900–7920. https://doi.org/10.1523/JNEUROSCI.0707-22.2022
https://www.scripps.edu/news-and-events/press-room/2022/20221019-cline-neuroscience.html
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