A combination of running and memantine increases neurogenesis and reduces activation of developmentally-born dentate granule neurons in rats

摘要

During hippocampal-dependent memory formation, sensory signals from the neocortex converge in the dentate gyrus. It is generally believed that the dentate gyrus decorrelates inputs in order to minimize interference between codes for similar experiences, often referred to as pattern separation. The proportion of dentate neurons that are activated by experience is therefore likely to impact how memories are stored and separated. Emerging evidence from mouse models suggests that adult-born neurons can both increase and decrease activity levels in the dentate gyrus. However, the conditions that determine the direction of this modulation, and whether it occurs in other species, remains unclear. Furthermore, since the dentate gyrus is composed of a heterogeneous population of cells that are born throughout life, newborn neurons may not modulate all cells equally. We aimed to investigate whether adult neurogenesis in rats regulates activity in dentate gyrus neurons that are born at the peak of early postnatal development. Adult neurogenesis was increased by subjecting rats to an alternating running and memantine treatment schedule, and it was decreased with a transgenic GFAP-TK rat model. Activity was measured by Fos expression in BrdU+ cells after rats explored a novel environment. Running + memantine treatment increased adult neurogenesis by only 17%, but completely blocked experience-dependent Fos expression. In contrast, GFAP-TK rats had a 68% reduction in adult neurogenesis but normal experience-dependent Fos expression. The inconsistent relationship between neurogenesis and Fos expression suggests that neurogenesis does not regulate DG activity during exploration of a novel environment. Nonetheless, running and memantine may benefit disorders where there is elevated activity in the dentate gyrus, such as anxiety and age-related memory impairments.