This project focuses on the interactions between experience and adult neurogenesis in the hippocampal region of the brain. We are interested in understanding how experiences, including positive and stressful experiences, regulate adult neurogenesis and how the new neurons alter responses in these situations. 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. We have previously found that specifically inhibiting adult neurogenesis in mice increases their response to stress, leading to enhanced caution, or anxiety-like behavior, in unpredictable threat situation. During the past year, we have asked whether adult neurogenesis affects behavior under positive, or rewarding, conditions as well as stressful, threatening conditions. To do this, we used transgenic rat and mouse lines that we developed that allow us to stop neurogenesis with no side effects by feeding the animals an antiviral drug. We trained these animals lacking adult neurogenesis, and sibling control animals with normal adult neurogenesis, to lever press for food rewards. We found that loss of new neurons had no effect on the animals ability to learn to lever press for rewards or on their preference for one reward over another. However, when animals had to work progressively harder for each successive reward, the animals lacking adult neurogenesis gave up sooner. And when animals could eat plain chow or work for rewarding food, the animals without new neurons earned fewer rewards. These effects were seen in both mice and rats. However, these effects were not observed when a highly preferred food reward was used in testing. Taken together, these findings suggest that adult neurogenesis does affect behavior under non-stressful, rewarding conditions. Specifically, the new neurons appear to enhance motivation to work for weak, but not strong, rewards. This phenotype appears similar to a human condition described as behavioral apathy.

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17
Fiscal Year
2018
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U.S. National Institute of Mental Health
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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
Soumier, Amelie; Carter, Rayna M; Schoenfeld, Timothy J et al. (2016) New Hippocampal Neurons Mature Rapidly in Response to Ketamine But Are Not Required for Its Acute Antidepressant Effects on Neophagia in Rats. eNeuro 3:
Snyder, Jason S; Grigereit, Laura; Russo, Alexandra et al. (2016) A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis. eNeuro 3:

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