Cellular activation of hypothalamic hypocretin/orexin neurons facilitates short-term spatial memory in mice

•Activation of HO neurons increases the expression of the activity marker c-Fos.•HO activation improves spatial short-term memory for novel locations.•Similar increases in HO activity had no effect on object recognition memory.

The hypothalamic hypocretin/orexin (HO) system holds a central role in the regulation of several physiological functions critical for food-seeking behavior including mnemonic processes for effective foraging behavior. It is unclear however whether physiological increases in HO neuronal activity can support such processes. Using a designer rM3Ds receptor activation approach increasing HO neuronal activity resulted in improved short-term memory for novel locations. When tested on a non-spatial novelty object recognition task no significant difference was detected between groups indicating that hypothalamic HO neuronal activation can selectively facilitate short-term spatial memory for potentially supporting memory for locations during active exploration.