Perfect balance: How the brain fine-tunes its sensitivity

We are constantly exposed to a wide range of sensory stimuli, from loud noises to whispers. In order to efficiently process these diverse stimulus intensities, the brain needs to strike a balance in its responsiveness. An excessive sensitivity triggers an over-activation of nerve cells in response to a stimulus, leading to epileptic seizures. Conversely, insufficient sensitivity results in a reduced ability to perceive and discriminate stimuli.

But how does the brain manage to be highly sensitive without becoming over-activated? "The key lies in maintaining a balance between neural excitation and inhibition," explains Professor Peter Scheiffele from the Biozentrum, University of Basel. "In mouse models, we have now discovered how this balance is maintained to ensure stable brain function." The study particularly focused on the neocortex, a brain area responsible for perception and a range of complex functions such learning.
Our brain consists of billions of interconnected nerve cells that interact through so-called synapses and process sensory stimuli such as sounds, touch, and sights. While excitatory neurons pass on the input signal, inhibitory neurons control the timing and intensity of the information flow. This internal control system ensures that the nervous system responds appropriately to stimuli.

Network over-activation and its link to epilepsy

Neurons are able to detect an elevated neuronal network activity and subsequently reduce the system's sensitivity to stimuli. But how the cells are instructed at the molecular level was poorly understood. "We have now revealed that highly activated excitatory neurons release a protein called BMP2," says lead author Dr. Zeynep Okur. "BMP2 signals to the inhibitory neurons, initiating a genetic program that leads to the formation of new synapses.” These additional synapses increase the impact of inhibitory neurons and dampen network activity.