Connectomics: Mapping the Brain
The human brain is filled with approximately 100 billion neurons, each of which makes a multitude of connections to neighboring neurons. The diversity of these neurons and vast interconnections facilitate processes such as those involved in decision making, evoking a memory, riding a bike, or simply reading this sentence. Incorrect wiring of these neurons may be the basis of some mental disorders and deficits. To understand how the structure of neural networks mediates function, researchers have emphasized the development of techniques to identify how every neuron is intimately connected to its neighbor neurons. And with this, the field of connectomics is born.
Connectomics is considered a branch of biotechnology that uses automated, high-speed imaging systems to construct detailed maps of neural circuits. This research effort is often compared to genomics, which is well known for the human genome project. As the human genome project sought to map and identify all of the genes in human DNA, connectomics seeks to identify and map all neural connections in the brain. In this respect, a detailed map of neural connections is referred to as a connectome.
In a particular approach to connectomics led by Jeff Lichtman’s lab at Harvard University, a small block of brain tissue is preserved in plastic, sliced into 30 nanometer sections by a very sharp blade, and collected onto silicon wafers, as illustrated in the figure below. Approximately 1000 sections can be collected per day. Next, the sections are imaged with an electron microscope at 5 nanometer/pixel resolution. Imaging a cubic millimeter of brain tissue requires one petabyte of storage space (106 gigabytes = 1000 terabytes = 1 petabyte)! With the current technology, it would take about 10 million years to map every synapse in a human brain, and would require several million more petabytes of data to store the information. As a comparison, this is roughly the same amount of data that has ever been created on the entire Internet!
Fortunately, we don’t have to wait 10 million years to begin to appreciate the type of information provided by connectomics. Examination of a partially reconstructed 100TB dataset acquired over 100 days reveals the complex neural wiring for a volume of brain tissue approximately the size of a grain of salt. Within a fully reconstructed 600 cubic micron volume of this dataset, exists over 600 axons, 40 dendrites, and 500 synapses with every synaptic vesicle accounted for. Watch this TED talk in which Jeff Lichtman shows us what connectomics data actually looks like (begin watching at minute 14):
[youtube=http://www.youtube.com/watch?v=F37kuXObIBU&t=14m2s&w=750]
Datasets with this level of detail have previously been considered too numerically complex to acquire and process. The advancements made in the field of connectomics are making this type of information a reality. Bottlenecks do still exist in the process flow, but technological advancements are steadily minimizing these impediments. For example, current image acquisition speeds run at about 1TB per day, but researchers project that in a few years, acquisition speeds will reach 3TB per hour; a 72-fold increase! As the catalogue of these datasets expands and encompasses more brain conditions, we may better understand how neurons form circuits to facilitate riding bikes, recalling memories, and gain further insights into the development of neural diseases.
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Written by Steven Walston
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References:
Grantz J. and Reinsel D. (2010). The Digital Universe Decade: Are You Ready? IDC http://www.emc.com/collateral/analyst-reports/idc-digital-universe-are-you-ready.pdf
Lichtman, J. (2013, January 31). Connectomics [Video file]. Retrieved from http://www.youtube.com/watch?v=F37kuXObIBU
Morgan J.L. and Lichtman J.W. (2013) Why Not Connectomics. Nature Methods, 10:494-500. DOI: 10.1038/nmeth.2480.
Vázquez-Reina A., Jeong W.K., Lichtman J. & Pfister H. (2011). The connectome project, XRDS: Crossroads, The ACM Magazine for Students, 18 (1) 8. DOI: 10.1145/2000775.2000782
Images adapted from neuroimages.tumblr.com and from Lichtman, J. (2013, January 31). Connectomics [Video file]. Retrieved from http://www.youtube.com/watch?v=F37kuXObIBU
