This study investigates the functional role of adult hippocampal neurogenesis in spatial pattern separation, a process crucial for forming distinct representations of similar inputs. Using adult mice with ablated neurogenesis through focal X-irradiation and lentiviral expression of dominant negative Wnt (dnWnt), researchers found that these mice exhibited specific impairments in spatial discrimination tasks. Mice with ablated neurogenesis were impaired in tasks where stimuli were presented with little spatial separation but performed normally when stimuli were widely separated. This suggests that newborn neurons are essential for normal pattern separation function in the dentate gyrus (DG) of adult mice. The study also highlights that the impairment is parameter-sensitive, indicating a critical threshold for the amount of neurogenesis required for optimal DG function. These findings provide experimental evidence for the role of newborn neurons in spatial pattern separation and suggest that immature neurons may contribute directly or indirectly to this process.This study investigates the functional role of adult hippocampal neurogenesis in spatial pattern separation, a process crucial for forming distinct representations of similar inputs. Using adult mice with ablated neurogenesis through focal X-irradiation and lentiviral expression of dominant negative Wnt (dnWnt), researchers found that these mice exhibited specific impairments in spatial discrimination tasks. Mice with ablated neurogenesis were impaired in tasks where stimuli were presented with little spatial separation but performed normally when stimuli were widely separated. This suggests that newborn neurons are essential for normal pattern separation function in the dentate gyrus (DG) of adult mice. The study also highlights that the impairment is parameter-sensitive, indicating a critical threshold for the amount of neurogenesis required for optimal DG function. These findings provide experimental evidence for the role of newborn neurons in spatial pattern separation and suggest that immature neurons may contribute directly or indirectly to this process.