Navigation and memory functions are essential for survival and are regulated by the hippocampus. One of the key modulators of hippocampal activity is the endocannabinoid system through the cannabinoid receptor type-1 (CB1). CB1 is widely expressed in various types of hippocampal cells. While it is known that CB1 participates in memory processes, its specific roles in different cell types and how these roles may differ between sexes remain unclear. This study investigates the cell- and sex-specific modulation of navigation and memory by CB1 receptors. To this end, we selectively deleted CB1 receptors from neurons or astrocytes from the hippocampus of adult male and female mice. We then assessed its effect on a comprehensive range of behaviors, including innate emotional responses, memory, navigation, and nesting.

Specific deletion of CB1 in CAMKII-expressing neurons produced a pronounced effect in males, leading to increased anxiety and impairments in both reference and spatial memory. These mice also showed altered performance in the Barnes maze, relying less on spatial strategies. By contrast, females were less affected by this specific deletion. Interestingly, deletion of CB1 from astrocytes led to spatial memory impairments in both males and females, which also showed reduced LTP and a decreased reliance on Spatial strategies in the Barnes maze. In conclusion, our findings show that neuronal CB1 receptors are critical for the spatial navigation strategy in males, while astrocytic CB1 receptors play a key role in memory processes both in males and females.

More information:

• https://www.achucarro.org/laboratory/cellular-basis-of-behavior-and-disease/