The Triple Helix @ UChicago

Spring 2014

"The BRAIN Initiative: From Imaging to Treatment" by Gustavo Pacheco

 

In April 2003 one of the greatest feats in human exploration was accomplished, the sequencing of the human genome.[1] The human genome was principally sequenced by the U.S. government and Celera Genomics. Despite having mapped out all the hereditary information, the question of how genes interact to yield various human processes is still a mystery. Researchers are challenged by the difficulties in understanding in how neurological processes yield thought, emotions and mental disease. This issue is shifting to approaches to understand the cellular interactions between individual neurons and interactions between parts of the brain mediated by molecular interactions. The U.S. Department of Health and Human Services is addressing this shift in research through the development of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative.[2] 

The BRAIN initiative seeks to encourage research that builds off maps of neural pathways which would prove to be useful in understanding the cellular connections that underlie thought and disease. In addition, the Gene Expression Nervous System Atlas (GENSAT)[3] was established to pictorially map specific cells using the expression of genes throughout the mouse central nervous system of genetically engineered mice. The BRAIN initiative has been developing the “connectome”, a project similar to the GENSAT. The connectome project seeks to map out the neural networks that are involved in human function on a neuron to neuron level.[4] The connectome will provide a better understanding of neural connectivity, how the whole brain is wired and the effects of different neural wirings. Discovering different neural circuits provides the hope of understanding how psychiatric and neuronal disorders develop. 

Developing a map like the connectome, requires advanced imaging techniques. One of these neurological mapping techniques is the brainbow. This technique tags individual cells using artificially constructed genes that express various fluorescent proteins.[5] Artificially constructed genes are formed by cutting and pasting components from different genes linked to a fluorescent portion. Therefore, a gene of interest is selected and a portion of a gene that encodes a brightly colored protein is inserted close to the gene of interest so wherever the gene of interest is transcribed and translated into a protein a fluorescent color would be present. Thus, localization and expression level could be known. This allows for the extensions of cells to be mapped and the contacts between them to be visualized. This has provided very impressive visual representations of neural networks. Such a novel technique, however, requires improvements in efficiency and cost effectiveness. The BRAIN initiative has provided funds to develop this neural imaging technology. 

The BRAIN initiative is currently developing specific goals for mapping the brain, and selecting research labs that can engineer technology to meet these goals. One of these goals is to understand the dynamic activity of neural circuits.[6] To realize this goal, the BRAIN initiative searches for technologies that can conduct large scale recordings and manipulations of neural activity to understand dynamic signals in the nervous system. Through the incorporation of the brainbow technology and other methods of essentially color coding neurons, we hope to obtain information about the complex neural networks present in the brain. This allows for the identification of miniscule differences in neural system circuitry that lead to the identification of dysfunction in cellular interactions present in mental health disorders. 

However, a major issue with these measurements is that it is difficult to conduct both temporal and spatial measurements simultaneously with great accuracy. The optimal technology seeks to reduce this problem pinpointing specific regions of neural circuitry and understand how components of the circuit function in relation to other circuits not only by their connections but how they interact over time. This is important in mental health research because to understand mental health disorders such as autism and epilepsy it is not enough to understand how neurons are connected, but also how they interact over time. Being able to understand both through imaging technologies of neural activity would allow for more targeted treatments.  

The BRAIN initiative seeks to build upon the research that has already been conducted in understanding the brain through mapping and funding current efforts. The BRAIN initiative has very promising objectives for revolutionizing the field of neuroscience through technological developments. The research that these new technologies can produce will allow us to understand the brain in radical new ways. 

References

[1] All About The Human Genome Project (HGP)." All About The Human Genome Project (HGP). N.p., n.d. Web. 10 May 2014. 
[2] "Brain Research through Advancing Innovative Neurotechnologies (BRAIN) - National Institutes of Health (NIH)." U.S National Library of Medicine. U.S. National Library of Medicine, n.d. Web. 11 May 2014. 
[3] "GENSAT Brain Atlas of Gene Expression in EGFP Transgenic Mice." GENSAT Brain Atlas of Gene Expression in EGFP Transgenic Mice. N.p., n.d. Web. 11 May 2014. 
[4] "NIH Blueprint for Neuroscience Research." The Human Connectome Project. N.p., n.d. Web. 11 May 2014. 
[5] Lichtman, Jeff W., Jean Livet, and Joshua R. Sanes. "A Technicolour Approach to the Connectome." Nature Reviews Neuroscience 9.6 (2008): 417-22. Print. 
[6] USA. Department of Health and Human Services. RFA-NS-14-007: BRAIN Initiative: New Technologies and Novel Approaches for Large-Scale
Recording and Modulation in the Nervous System (U01). NIH, n.d. Web. 11 May 2014. 

 
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