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.
In this study, the researchers wanted to see how activation of these inhibitory neurons would influence how the brain processes visual input — in this case, horizontal, vertical or tilted bars. When such a stimulus is presented, individual cells in the eye respond to points of light, then convey that information to the thalamus, which relays it to the visual cortex. The information stays spatially encoded as it travels through the brain, so a horizontal bar will activate corresponding rows of cells in the brain.
Those cells also receive inhibitory signals, which help to fine-tune their response and prevent overstimulation. The MIT team found that these inhibitory signals have two distinct effects: Inhibition by SOM neurons subtracts from the total amount of activity in the target cells, while inhibition by PV neurons divides the total amount of activity in the target cells.
“Now that we finally have the technology to take the circuit apart, we can see what each of the components do, and we found that there may be a profound logic to how these networks are naturally designed,” Wilson says.
These two types of inhibition also have different effects on the range of cell responses. Every sensory neuron responds only to a particular subset of stimuli, such as a range of brightness or a location. When activity is divided by PV inhibition, the target cell still responds to the same range of inputs. However, with subtraction by SOM inhibition, the range of inputs to which cells will respond becomes narrower, making the cell more selective.
Increased inhibition by PV neurons also changes a trait known as the response gain — a measurement of how much cells respond to changes in contrast. Inhibition by SOM neurons does not alter the response gain.
The researchers believe this type of circuit is likely repeated throughout the brain and is involved in other types of sensory perception, as well as higher cognitive functions.
Sur’s lab now plans to study the role of PV and SOM inhibitory neurons in a mouse model of autism. These mice lack a gene called MeCP2, giving rise to Rett Syndrome, a rare disease that produces autism-like symptoms as well as other neurological and physical impairments. Using their new technology, the researchers plan to test the hypothesis that a lack of neuronal inhibition underlies the disease.