Inhibitory Mechanisms Of Homeostatic Plasticity In Vivo (360G-Wellcome-212264_Z_18_Z)

Homeostatic plasticity is the compensatory mechanisms that regulate activity levels in the brain during ongoing changes, for example following learning or input loss. To date, homeostatic plasticity studies have largely focused on changes in excitatory neurons; however, inhibitory neurons also play an important role in regulating overall network activity. Given the known connectivity of excitatory and inhibitory neurons in mouse visual cortex, changing activity in different inhibitory subtypes would have drastically different effects on network activity, but the role of specific inhibitory subtypes in homeostatic plasticity is unclear. We will use in vivo two-photon imaging in behaving adult mice expressing genetically encoded calcium indicators to measure the activity levels of inhibitory subtypes during the homeostatic recovery of activity that follows the loss of sensory input to the visual cortex. We will then use optogenetic tools to change activity levels in these inhibitory subtypes, to determine: 1) their causal role in the maintenance of activity after homeostatic activity recovery, and 2) their interactions with homeostatic plasticity mechanisms that facilitate homeostatic recovery. These experiments will identify which inhibitory subtypes are critical for homeostatic plasticity.