Cortical plasticity: it's time to get excited about inhibition

Research from Brandeis University published online this week in Nature offers new insight into how neural circuits are shaped by experience. The article provides new evidence for the mechanisms that affect the ability of the visual cortex to plastically rearrange itself following periods of visual deprivation.

“Getting our brains to wire up properly requires experience during an early critical period of development, and understanding the mechanisms of this experience-dependent plasticity is critical for understanding human development, its disorders, and for designing strategies that promote optimal cognitive development during early childhood,” explained author and neuroscientist Gina Turrigiano.

Neuroscientists have long known that the brain needs proper sensory stimulation to develop correctly and that experience can induce plastical changes in the functional architecture of sensory cortices. Animals that grow up with one eye covered during a critical period of brain development lose some of their visual acuity and ability to respond to certain visual stimuli. In these experimental conditions, Turrigiano and colleagues explored the visual cortex circuit of young rats by recording electrical activity of neurons and their connections.

“We have found an important and novel mechanism involved in the loss of function of cortical circuits,” said co-author neurophysiologist Arianna Maffei. “While our results directly apply to the loss of visual function secondary to sensory deprivation, they very likely represent a more general strategy for cortical networks to respond to experience.”

The researchers showed that the lasting cortical shut-down induced by visual deprivation at early stages of development is the result of a massive increase of cortical inhibition. Specifically, the strength of inhibitory synaptic connections between two types of neurons in the layer receiving the input – the inhibitory fast-spiking basket cells and the excitatory star pyramidal neurons – increased 3-fold.

While it has been historically believed that regulation of excitatory synapses is most critical to the development of neuronal circuitry, and that loss of function is the result of a depression of excitation, this research demonstrates that inhibitory synapses play a critical role in proper network wiring and ultimately in preserving – or disrupting – neuronal function.

“Our data suggest a major revision of thinking about how experience works on our brains,” noted Turrigiano. “Instead of targeting exclusively excitatory networks, a major locus of plasticity lies within the inhibitory networks. Our data show that inhibitory networks within the cortex are highly plastic, and that some pathological states arise through inappropriate activation of inhibitory plasticity.”