Inhibitory Mechanisms Of Homeostatic Plasticity In Vivo

The brain’s inhibitory neurons—cells that dampen activity—are the missing piece in understanding how neural networks stabilise themselves after learning or sensory loss. Most research on homeostatic plasticity has focused on excitatory neurons, the cells that fire to transmit signals. But inhibitory neurons, which counterbalance that firing, are equally critical for keeping brain activity within a healthy range. In the mouse visual cortex, different subtypes of inhibitory neurons connect to excitatory cells in distinct ways, so altering one subtype could have very different effects on the network than altering another. Which subtypes actually drive the brain’s compensatory response is unknown. This project will use two-photon calcium imaging in behaving adult mice to track the activity of specific inhibitory subtypes as the visual cortex recovers from lost sensory input. Optogenetics will then allow the researchers to selectively increase or decrease activity in those subtypes, testing whether they are causally required for maintaining stable activity after recovery. This is fundamental science with no immediate clinical application. However, homeostatic plasticity is thought to go awry in epilepsy, chronic pain, and certain neurodevelopmental disorders. Identifying the inhibitory subtypes that govern this process could eventually point toward more targeted ways to restore balance in hyperactive or unstable neural circuits.