An electron microscopy-based reconstruction of a cubic millimeter of cortex has been generated by Google’s Connectomics team and Harvard researchers. The 3D map, from a patient with epilepsy, extends through all cortical layers, is the volume of about one-millionth of a whole brain—smaller than a grain of rice. It contains roughly 57,000 cells, 150 million synapses, 230 millimeters of blood vessels and incorporates 1.4 petabytes of data that is freely available.
The study was published in Science and its lead author is Alexander Shapson-Coe of the department of molecular and cellular biology at Harvard University.
The human brain contains an estimated 100 billion neurons and over 100 trillion synaptic connections. Access to high-quality human brain tissue has been a key hurdle to studying human neural circuits. Brain biopsies are rarely done except on cancers, so they aren’t so helpful for investigating the normal human brain. Brain organoids are being used, but their cortical layers are not yet representative.
But as these researchers write, “Connectomic imaging approaches are now available to render neural circuits of sufficiently large volume and high enough resolution to study the connectivity at the level of individual neurons and their synaptic connections but over a scale comprising thousands of neurons.”
This group decided to use human brain tissue that is a by-product of neurosurgical procedures to study normal—and ultimately disordered—human neural circuits. Aided by machine learning tools from Google Research, the Harvard team traced brain cells at nanoscale levels. They imaged this sample by high-throughput serial section electron microscopy, generating a petascale dataset that was analyzed with new tools and computationally intensive methods. Their database was first released as a preprint paper in 2021.
For this study, the team took a tiny bit of brain tissue from a 45-year-old woman with epilepsy during surgery. The Harvard team then sliced the sample into 5,019 cross sections roughly 30 nanometers thick. They then imaged the slices with an electron microscope, capturing nanoscale cellular details.
Connectomic imaging approaches are now available to render neural circuits of sufficiently large volume and high enough resolution to study the connectivity at the level of individual neurons and their synaptic connections but over a scale comprising thousands of neurons. Generating such a dataset was the goal of this project.
The team reconstructed thousands of neurons, more than a hundred million synaptic connections, and other tissue elements, including glial cells, the blood vasculature, and myelin.
Among their findings were a previously unrecognized class of directionally oriented neurons in deep layers and very powerful and rare multisynaptic connections between neurons throughout the sample.
The researchers believe this work provides evidence of the feasibility of human connectomic approaches to visualize and ultimately gain insight into the physical underpinnings of normal and disordered human brain function.
They write, “This work provides evidence of the feasibility of human connectomic approaches to visualize and ultimately gain insight into the physical underpinnings of normal and disordered human brain function.”
