The most comprehensive circuit diagram of neurons in a mammalian brain has been created by scientists, providing groundbreaking insights into the mystery of how the brain works.
The map is of a speck of a mouse’s visual cortex, smaller than a grain of sand, and traces the structure of 84,000 neurons linked by half a billion synapses and approximately 5.4km of neuronal wiring. The 3D reconstruction of the cubic millimetre of brain is helping uncover how the brain is organised and how different cell types work together, and could have implications for the understanding of intelligence, consciousness and neuronal conditions such as Alzheimer’s, Parkinson’s, autism and schizophrenia.
The advances are “a watershed moment for neuroscience, comparable to the Human Genome Project in their transformative potential”, according to Dr David Markowitz, former programme manager of the US governmental organisation Intelligence Advanced Research Projects Activity (IARPA), who coordinated the work.
The MICrONS project sought not only to map the structure of neurons, but also investigated the electrical signalling between then, showing how they communicate and providing a better picture of the hidden conversations in the brain.
Scientists at Baylor College of Medicine in Texas began by using specialised microscopes to record the brain activity from the target region as the animal watched various movies and YouTube clips. Afterwards, Allen Institute researchers took that same cubic millimetre of the brain and sliced it into more than 25,000 layers, each 1/400th the width of a human hair, and used an array of electron microscopes to take high-resolution pictures of each slice.
Finally, another team at Princeton University used artificial intelligence and machine learning to reconstruct the cells and connections into a 3D volume. Combined, the massive data set is 1.6 petabytes in size, equivalent to 22 years of non-stop HD video.
“Inside that tiny speck is an entire architecture like an exquisite forest,” said Dr Clay Reid, senior investigator and a neurobiologist at the Allen Institute. “It has all sorts of rules of connections that we knew from various parts of neuroscience, and within the reconstruction itself, we can test the old theories and hope to find new things that no one has ever seen before.”
The findings reveal new cell types and a new principle of inhibition within the brain. Scientists previously thought of inhibitory cells – those that suppress neural activity – as a simple force that dampens the action of other cells. But the latest work found that inhibitory cells are highly selective about which cells they target, creating a network-wide system of coordination and cooperation.
Understanding the brain’s form and function could pave the way for a better understanding of brain disorders involving disruptions in neural communication.
“If you have a broken radio and you have the circuit diagram, you’ll be in a better position to fix it.” said Dr Nuno da Costa, associate investigator at the Allen Institute. “We are describing a kind of Google map or blueprint of this grain of sand. In the future, we can use this to compare the brain wiring in a healthy mouse to the brain wiring in a model of disease.”
The findings are published in a series of papers in the journal Nature.
