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 behavioral effects that persist long after a stressful experience. To do this, we used transgenic rats that we developed to allow us to stop neurogenesis with no side effects by feeding the animals an antiviral drug. We exposed these animals lacking adult neurogenesis, and sibling control animals with normal adult neurogenesis, to multiple stressors on a single day. We found that loss of new neurons had no effect on the rats behavior shortly at short time points: two weeks after the stressful experience, all rats increased their anxietylike behavior and their preference for familiar locations regardless of the presence or absence of new neurons. However, one month after the stressful experience, rats with ongoing neurogenesis behaved as if they had never been stressed, while rats that lacked new neurons continued to show elevated anxietylike behavior and stress hormone levels. Mirroring the changes in anxiety-like behavior, the size of the ventral CA1 region of the hippocampus shrank in all rats exposed to stress at the early time point and then recovered only in control rats with intact adult neurogenesis. Together, these findings suggest that new neurons are important for recovery of normal behavior and hippocampal structure following a stressful experience and point to the ventral CA1 region as a potential mediator of stressinduced anxietylike behavior.
| 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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