Inhibitory maturation and ocular dominance plasticity in mouse visual cortex require astrocyte CB1 receptors

Summary: Endocannabinoids, signaling through the cannabinoid CB1 receptor (CB1R), regulate several forms of neuronal plasticity. CB1Rs in the developing primary visual cortex (V1) play a key role in the maturation of inhibitory circuits. Although CB1Rs were originally thought to reside mainly on presynaptic axon terminals, several studies have highlighted an unexpected role for astrocytic CB1Rs in endocannabinoid mediated plasticity. Here, we investigate the impact of cell-type-specific removal of CB1Rs from interneurons or astrocytes on development of inhibitory synapses and network plasticity in mouse V1. We show that removing CB1Rs from astrocytes interferes with maturation of inhibitory synaptic transmission. In addition, it strongly reduces ocular dominance (OD) plasticity during the critical period. In contrast, removing interneuron CB1Rs leaves these processes intact. Our results reveal an unexpected role of astrocytic CB1Rs in critical period plasticity in V1 and highlight the involvement of glial cells in plasticity and synaptic maturation of sensory circuits.