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Unraveling the Connections of the Brain

brain hat

Yes it’s a brain hat, and yes I do want one!!

The brain is complex, heck if it wasn’t then we wouldn’t be smart enough to figure out how it works. I guess it’s one of those stupid catch-22 type things. Still, little is known about how the brain forms connections and the process that is behind all that. Thankfully new research provides an important glimpse into the processes that establish connections between nerve cells in the brain. These connections [also known as synapses] allow nerve cells to transmit and process information involved in thinking and moving the body. Sounds simple enough, but the formation is quite complex.

The finding is, of course, an important step forward in efforts to learn how the developing brain is built. This is an area of research essential to understanding the causes of things like intellectual disability and autism, or even cooler growing actual brains [but maybe that’s just me].

“We now are looking at how loss of this wiring affects brain function in mice,” said senior author Azad Bonni, MD, PhD, the Edison Professor of Neurobiology and head of the Department of Anatomy and Neurobiology at the School of Medicine.

The team is studying synapses in the cerebellum, a region of the brain that sits in the back of the head. The cerebellum plays a central role in controlling the coordination of movement and is essential for what researchers call procedural motor learning, the thing that makes it possible to move our muscles at an unconscious level, such as when we ride a bicycle or play the piano [… poorly,like me].

“The cerebellum also regulates mental functions,” Bonni said. “So, impairment of the wiring of nerve cells in the cerebellum may contribute to movement disorders as well as cognitive problems including autism spectrum disorders.”

The new results show that a complex of proteins known as NuRD [ the short term for nucleosome remodeling and deacetylase] plays a fairly high supervisory role in some aspects of the cerebellum’s construction. When the researchers blocked the NuRD complex, cells in the cerebellum called granule cells failed to form connections with other nerve cells, the Purkinje neurons [named after the guy who discovered them, hence the weird sounding name]. These circuits are important for the cerebellum’s control of movement coordination and learning.

The team showed that NuRD exerts influence at the epigenetic level, which means it controls factors other than DNA that affect gene activity. For example, NuRD affects the configurations of molecules that store DNA and that can open and close the coils of DNA like an accordion, making genes less or more accessible. Changing the accessibility of genes changes their activity levels. A good example of this, cells can’t frequently make proteins from genes in a tightly packed coil of DNA [because they need access to the DNA to read it in order to make the protein].

NuRD also alters tags on the proteins that store DNA, decreasing the chances that the gene will be used. Among the genes deactivated by NuRD are two that control the activity of other genes involved in the wiring of the cerebellum.

“This tells us that the NuRD complex is very influential—not only does it affect the activity of genes directly, it also controls other regulators of multiple genes,” Bonni said.

Yeah it sounds simple enough, NuRD controls genes, which thus control formation of connections to other cells. But things like this are the basic building blocks scientists need to know in order to figure out what goes wrong when the brain is formed. Findings like this one are the cornerstone to solving bigger mysteries like autism and any other mental disorder.

Bonus if you pronounced NuRD as nerd! If you did [and even if you didn’t] then you can have the full study, which can be found —here!

Yamada, T., Yang, Y., Hemberg, M., Yoshida, T., Cho, H., Murphy, J., Fioravante, D., Regehr, W., Gygi, S., Georgopoulos, K., & Bonni, A. (2014). Promoter Decommissioning by the NuRD Chromatin Remodeling Complex Triggers Synaptic Connectivity in the Mammalian Brain Neuron, 83 (1), 122-134 DOI: 10.1016/j.neuron.2014.05.039

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