Layer specific regulation of critical period timing and maturation of mouse visual cortex by endocannabinoids

Plasticity during the critical period is important for the functional maturation of cortical neurons. While characteristics of plasticity are diverse among cortical layers, it is unknown whether critical period timing is controlled by a common or unique molecular mechanism among them. We here clarified layer-specific regulation of the critical period timing of ocular dominance plasticity in the primary visual cortex. Mice lacking the endocannabinoid synthesis enzyme diacylglycerol lipase-α exhibited precocious critical period timing, earlier maturation of inhibitory synaptic function in layers 2/3 and 4, and impaired development of the binocular matching of orientation selectivity exclusively in layer 2/3. Activation of cannabinoid receptor restored ocular dominance plasticity at the normal critical period in layer 2/3. Suppression of GABAA receptor rescued precocious ocular dominance plasticity in layer 4. Therefore, endocannabinoids regulate critical period timing and maturation of visual function partly through the development of inhibitory synaptic functions in a layer-dependent manner. [Display omitted] •Mice lacking DGL-α exhibit precocious critical period in L2/3 and 4 of visual cortex•DGL-α KO exhibits impaired binocular matching of orientation selectivity in L2/3•DGL-α KO exhibits earlier maturation of inhibitory synaptic function in L2/3 and 4•Suppression of GABAA receptor rescues precocious ocular dominance plasticity in L4 Natural sciences; Biological sciences; Physiology; Neuroscience; Developmental neuroscience; Systems neuroscience; Sensory neuroscience