Raphael Thys
Six layers of excitatory neurons color-coded by depth. (Credit: Google Research and Lichtman Lab)
CAMBRIDGE, Mass. — Scientists often compare the human brain to a giant computer. However, an amazing new study is revealing just how more advanced our brains are than the device sitting on your desk! Researchers from Harvard University and Google worked together to map just one cubic millimeter of the human brain. In that microscopic section of the brain, the team found more data than what thousands of modern laptops are capable of storing!
Your brain is one of the most complex structures known to science. In that tiny cube of brain tissue, researchers discovered 57,000 neurons, 230 millimeters of blood vessels, and an astonishing 150 million connections between brain cells called synapses. The data contained within that minuscule piece of cortex from the temporal lobe amounts to a staggering 1,400 terabytes! To put that into perspective, the average PC user may have one terabyte of storage space in their device.
In this landmark study published this week in Science, the Harvard and Google teams mapped out one of these intricate million-synapse brain fragments in greater detail than ever before. It’s the largest complete 3D reconstruction of a neural circuit from a human brain to date.
“The word ‘fragment’ is ironic,” explains Professor Jeff Lichtman, the study’s lead author who was just appointed as Harvard’s new Dean of Science, in a media release. “A terabyte is, for most people, gigantic, yet a fragment of a human brain — just a minuscule, teeny-weeny little bit of human brain — is still thousands of terabytes.”
A range of histological features in 1 mm3 of the human brain was rendered, including neuropil (A) and its segmentation (B) at nanometer resolution, annotated synapses (C), excitatory neurons (D), inhibitory neurons (E), astrocytes (F), oligodendrocytes (G), myelin (H), and blood vessels (I). A previously unrecognized neuronal class (J) and multisynaptic connections (K) were also identified. (Credit: Science)
The map reveals the labyrinthine wiring diagram of each neuron and how they are connected, with some interesting surprises. The researchers spotted a rare configuration of super-connected cells, with a single axon (the long projecting fiber that neurons use to send signals) forming synapses with up to 50 others. They also found some axons taking strange twisting paths, forming “whorls” for reasons unknown.
The sample was taken from a patient with epilepsy, so the researchers don’t know if these unusual structures have a link to the condition or if they’re just random neurological quirks. Lichtman notes that scientists need a comprehensive reference atlas of how the brain works before they can start looking at what changes diseases cause.
That’s the overarching goal of his field called “connectomics” – to create complete neural wiring diagrams that reveal how trillions of synaptic connections give rise to our thoughts, behaviors, and brain disorders. Building these maps is a mind-bogglingly complex task the researchers have been chipping away at for nearly a decade in collaboration with AI experts from Google.
Using powerful algorithms trained on the team’s prior brain imaging data, Google’s software is able to trace out each individual 3D neuronal branch and automatically color-code the map into distinct cells. The researchers have also released user-friendly tools for other scientists to explore and annotate the connectome data.
“Given the enormous investment put into this project, it was important to present the results in a way that anybody else can now go and benefit from them,” says Google collaborator Viren Jain.
The newly published mouse cortex circuit marks an important milestone, but it’s just the tip of the iceberg in brain research. To comprehensively map an entire mouse brain at this high synapse-resolving resolution would require replicating their effort as much as 1,000 times over.
That’s the team’s next big goal, funded by the BRAIN Initiative from the National Institutes of Health. They plan to target the hippocampus formation, a brain region responsible for memory and involved in neurological diseases like Alzheimer’s. Completing a whole-brain neural wiring project in both mice and humans could open up countless breakthroughs in brain science and medicine.
Just as the Human Genome Project transformed biology by finally mapping our genes, Lichtman believes mapping the brain’s neural circuits will be critical for understanding how things go wrong in conditions ranging from autism to schizophrenia to traumatic brain injuries.