Age-Dependent Area-, Lamina- and Cell-Type-Specific Distribution of the Cannabinoid Type 1 Receptor in the Mouse...

The efficient processing of visual information relies on a mature visual cortex, characterized by hierarchically organized areas and a broad diversity of inhibitory and excitatory neurons. A tightly regulated excitation-inhibition (E/I) balance is essential for the optimal processing of visual inputs. A known regulator of the cortical E/I balance is the endocannabinoid (ECB) system, which relies on the cannabinoid type-1 receptor (CB1R) to perform its functions. To better understand the embedding of the CB1R in the neuronal networks of the visual cortex in adolescence and adulthood, we characterized the distribution of the receptor protein and its mRNA (cnr1) across layers, areas, and interneuron subtypes. We describe a specific laminar distribution of CB1R in the mature visual cortex along the full extent of the rostrocaudal brain axis. Moreover, cnr1 is expressed in the three main nonoverlapping subtypes of interneurons and is predominantly enriched in the 5ht3ar subtypes. Comparison of adolescent and adult visual cortex revealed a higher number of cnr1+ reelin interneurons in layer 1 and a lower number of cnr1+ somatostatin interneurons in layer 4 of the primary visual cortex (V1) in adolescence compared with adulthood. Overall, our findings confirm a distinct distribution of the receptor in V1 compared with higher-order visual areas based on a lower CB1R expression in layer 4, a broad cnr1 expression across cortical interneurons in key locations of top-down modulation, and a still immature ECB system in adolescence, making it potentially vulnerable to exogenous cannabinoids during this life period.