We study the regulation and function of adult neurogenesis in rats and mice, which show continued production of new neurons throughout adulthood similar to that in primates, including humans. During the past year, we have completed a study comparing adult neurogenesis in rats, a species commonly used for behavioral experiments, with that in mice, which are becoming increasingly prevalent in neuroscience research, as in all biomedical research, due to the availability of transgenic mouse lines. Studies of adult neurogenesis have been done in both species, and we wondered whether some apparently inconsistent results could be explained by differences in adult neurogenesis across the two species. We examined the number, maturation rate, behavioral activation, and functional importance of new neurons in mice and rats. We found that cell proliferation produces 3 times as many neuronal progenitors in rats than in mice. However, since the rat dentate gyrus is larger than, and contains approximately 3 times as many granule cells as, the mouse dentate gyrus, the production of new cells relative to the total population was equivalent in the two species. Many newborn cells die in both species during the first 4 weeks after they are generated, but twice as many cells survived in rats as in mice (60% versus 30%). During this period of cell death, new granule cells mature, downregulating their expression of several immature markers, upregulating expression of mature neuronal markers, and developing the ability to become activated and express immediate-early gene responses. All of these changes occurred 1-2 weeks later in new granule cells in mice than in rats. To look at activation of the young cells by a physiologically-relevant stimulus, we trained animals in a hippocampus-dependent spatial task and determined how many granule cells of each age were activated by the task. In rats, behavioral activation of granule cells peaked at 3 weeks of age, when 25% of granule cells of this age were activated, and then declined to 5% of cells activated at 10 weeks. In mice, 5% of granule cells were also activated at 10 weeks of age, but younger granule cells did not show increased activation in mice as they did in rats. To determine whether this species difference in activation of adult-born granule cells is paralleled by a critical role for new neurons in behavior, we stopped neurogenesis in adulthood using cranial irradiation and tested the animals in a spatial memory task. We found that rats developed deficits in this task over 4 weeks, while mice never showed behavioral deficits, even 8 weeks after irradiation. These findings indicate that new neurons are more numerous, faster maturing, and more important for behavior in rats than in mice. Taken together, they reconcile several confusing disagreements in the literature and suggest that future studies of the function of adult neurogenesis may be more successful in rats than in mice.
| Kempermann, Gerd; Gage, Fred H; Aigner, Ludwig et al. (2018) Human Adult Neurogenesis: Evidence and Remaining Questions. Cell Stem Cell 23:25-30 |
| Cameron, Heather A; Schoenfeld, Timothy J (2018) Behavioral and structural adaptations to stress. Front Neuroendocrinol 49:106-113 |
| Karlsson, Rose-Marie; Wang, Alice S; Sonti, Anup N et al. (2018) Adult neurogenesis affects motivation to obtain weak, but not strong, reward in operant tasks. Hippocampus 28:512-522 |
| Lin, Lin; Murphy, Jonathan G; Karlsson, Rose-Marie et al. (2018) DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral Impairments in Recognition, Learning and Memory. Front Cell Neurosci 12:84 |
| Pothayee, Nikorn; Cummings, Diana M; Schoenfeld, Timothy J et al. (2017) Magnetic resonance imaging of odorant activity-dependent migration of neural precursor cells and olfactory bulb growth. Neuroimage 158:232-241 |
| Schoenfeld, Timothy J; McCausland, Hayley C; Morris, H Douglas et al. (2017) Stress and Loss of Adult Neurogenesis Differentially Reduce Hippocampal Volume. Biol Psychiatry 82:914-923 |
| Akins, Michael R; Berk-Rauch, Hanna E; Kwan, Kenneth Y et al. (2017) Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains. Hum Mol Genet 26:192-209 |
| Glover, Lucas R; Schoenfeld, Timothy J; Karlsson, Rose-Marie et al. (2017) Ongoing neurogenesis in the adult dentate gyrus mediates behavioral responses to ambiguous threat cues. PLoS Biol 15:e2001154 |
| Schoenfeld, Timothy J; McCausland, Hayley C; Sonti, Anup N et al. (2016) Anxiolytic Actions of Exercise in Absence of New Neurons. Hippocampus 26:1373-1378 |
| Opendak, Maya; Offit, Lily; Monari, Patrick et al. (2016) Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis. J Neurosci 36:7027-38 |
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