Rapid critical period induction by tonic inhibition in visual cortex

Area of Science:

• Neuroscience
• Neurobiology
• Visual System Plasticity

Background:

• Ocular dominance plasticity, a model for experience-dependent cortical changes, typically requires intact GABAergic inhibition.
• Mice lacking glutamic acid decarboxylase 65 (GAD65), a key enzyme for GABA synthesis, show impaired ocular dominance plasticity.

Purpose of the Study:

• To investigate the precise timing requirements for GABAergic transmission in triggering experience-dependent plasticity.
• To understand how intracortical inhibition initiates changes in the visual cortex.

Main Methods:

• Monocular deprivation (MD) was applied to GAD65 knockout mice for 4 days.
• Diazepam (DZ), a benzodiazepine that enhances GABAergic transmission, or vehicle was infused daily before and/or during MD.
• Extracellular single-unit recordings were conducted in the visual cortex to assess neuronal responses.

Main Results:

• A minimum of 2 days of diazepam treatment near the start of MD was sufficient to restore ocular dominance plasticity, even without direct overlap with deprivation.
• Delayed diazepam infusion led to a loss of plasticity, associated with improved intrinsic inhibitory circuit function.
• Diazepam treatment in wild-type mice shortly after eye opening prematurely closed the critical period for plasticity.
• In dark-reared wild-type mice, diazepam also closed the critical period, while light exposure did not.

Conclusions:

• Enhanced tonic signaling via GABA(A) receptors can rapidly establish a state permissive for plasticity within the neocortex.
• This GABAergic signaling can trigger a critical period for ocular dominance plasticity independently of visual experience.
• The timing and duration of GABAergic signaling are crucial for initiating and regulating critical period plasticity.