Discovery of how some neurons inhibit others could shed light on autism, other neurological disorders.
The brain has billions of neurons, arranged in complex circuits that allow us to perceive the world, control our movements and make decisions. Deciphering those circuits is critical to understanding how the brain works and what goes wrong in neurological disorders.
MIT neuroscientists have now taken a major step toward that goal. In a new paper appearing in the Aug. 9 issue of Nature, they report that two major classes of brain cells repress neural activity in specific mathematical ways: One type subtracts from overall activation, while the other divides it.
“These are very simple but profound computations,” says Mriganka Sur, the Paul E. Newton Professor of Neuroscience and senior author of the Nature paper. “The major challenge for neuroscience is to conceptualize massive amounts of data into a framework that can be put into the language of computation. It had been a mystery how these different cell types achieve that.”
The findings could help scientists learn more about diseases thought to be caused by imbalances in brain inhibition and excitation, including autism, schizophrenia and bipolar disorder.
Lead authors of the paper are grad student Caroline Runyan and postdoc Nathan Wilson. Forea Wang ’11, who contributed to the work as an MIT undergraduate, is also an author of the paper.
A fine balance
There are hundreds of different types of neuron in the brain; most are excitatory, while a smaller fraction are inhibitory. All sensory processing and cognitive function arises from the delicate balance between these two influences. Imbalances in excitation and inhibition have been associated with schizophrenia and autism.
“There is growing evidence that alterations in excitation and inhibition are at the core of many subsets of neuropsychiatric disorders,” says Sur, who is also the director of the Simons Center for the Social Brain at MIT. “It makes sense, because these are not disorders in the fundamental way in which the brain is built. They’re subtle disorders in brain circuitry and they affect very specific brain systems, such as the social brain.”
In the new Nature study, the researchers investigated the two major classes of inhibitory neurons. One, known as parvalbumin-expressing (PV) interneurons, targets neurons’ cell bodies. The other, known as somatostatin-expressing (SOM) interneurons, targets dendrites—small, branching projections of other neurons. Both PV and SOM cells inhibit a type of neuron known as pyramidal cells.
To study how these neurons exert their influence, the researchers had to develop a way to specifically activate PV or SOM neurons, then observe the reactions of the target pyramidal cells, all in the living brain.