The Inner Workings of the Brain: Watch a Single Brain Cell Searching for Connections in This Viral Video

“We are basically treating a brain circuit as a computer and asked three questions: What does the circuit do? What is the wiring? Clay Reid, a senior investigator at Allen Institute and one the leading scientists of MICrONS, said: “What is the program?” “Experiments were performed to see neurons’ activity and to watch them calculate. We’re now able to see the components of the neural circuit. This network must be understood in order to understand the brain’s program.

These include the wiring and brain cells

It is possible to trace the wires between cells to create a map. This dataset joins other recent wiring diagrams taken from fruit flies and human brains using the same technology, electron microscopy. This technique reveals amazing details of an entire microscopic environment in this instance, the densely packed topography made up of tendrilled neurons and astrocytes as well as the tiny internal components of every cell.

The MICrONS dataset contains the largest number of cells and connections. It is large enough that it can capture complete local circuits as well as near-complete 3-D shapes for individual mouse neurons. This dataset doesn’t fully capture the long-distance connections made by some neurons. The cubic millimeter volume was chosen because it captures circuits from multiple brain areas that are involved in vision and also the structure of as many neurons as possible.

Baylor’s research team captured the activity of neurons in this area of the brain before the structural data could be gathered. This was done while the mouse viewed pictures or movies of natural scenes. “The neocortex is home to billions upon trillions of neurons that communicate through trillions of connections, which has given mammals extraordinary abilities. Andreas Tolias is a Baylor College of Medicine professor of neuroscience and director of the Center for Neuroscience and Artificial Intelligence. He was also one of the MICrONS’s lead scientists. “This program is exceptional because it allowed us to gather an interdisciplinary group to conduct a very ambitious experiment that will allow us to answer this question.”

The Baylor experiment was over, and Allen Institute researchers saved the brain in 27,000 slices. Each slice was only 40 nanometers thick. They also captured 150 million images using custom electron microscopes. For 12 days, the cutting process was monitored by teams of engineers, biologists, and software developers who were on standby to watch the machine in order to stop or restart it if necessary.

The Princeton team then used deep learning to “segment”, defining each cell individually and its internal components. Princeton’s software engineers, students, and postdocs used convolutional nets that were painstakingly learned over months to align serial section images into a 3-D stack of images, identify synaptic partners, and detect neuronal boundaries. Each step was distributed across supercomputers that ran for days at a stretch.

The result was beautiful digital renderings of over 200,000 brain cells, and their connections, which are intricate and complex. Many of these were never captured in their entirety before.

Seung said, “I feel privileged that I have worked with such a great team at Princeton and our outstanding partners from the Baylor College of Medicine & the Allen Institute.” We have been rewarded with amazing new vistas of the cortex. We are now moving into a new phase in our discovery process. As such, we are investing our efforts in building a community that will use the data in many different ways. Most of these we can’t predict. Only the collective efforts and collaboration of a group can unlock the potential of the resource to enable new discoveries about the brain.

Seung is joined by Kai Li, Princeton’s Paul M. Wythes’55 Professor in Computer Science and Marcia R. Wythes’86 Professor in Computer Science; graduate student Alexander Bae, Shanka Subhra Moondal, Sergiy Popovych and Nicholas Turner; Eric Anthony Mitchell of Class of 2018; current research scholars Ran Lu, Shang Mu; senior researcher Szi-Chieh Yu and Manuel Castro.