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 learning or stressful experiences, regulate adult neurogenesis and how the new neurons alter responses to stress and learning 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 hormonal and behavioral responses to stress, producing increased depressive-like behavior. Hippocampal function varies along its dorsoventral axis: the ventral pole plays a greater role in emotional behaviors, while the dorsal pole appears to be more important for spatial learning and memory. We have previously found that the new neurons in the ventral hippocampus are more active than those in the dorsal hippocampus during spatial water maze learning, even though new neurons are more numerous in the dorsal hippocampus. During the past year, we therefore examined the maturation of new neurons in different portions of the dentate gyrus. We found that the increased number of neurons added to the dorsal portion of the dentate gyrus is due to greater initial production of new cells (cell division), in this region with similar rates of survival of new cells in the dorsal and ventral poles. We also studied the time course of neuronal maturation in the two regions and found that new neurons in the dorsal pole are capable demonstrating neuronal activation in 2-3 weeks, which is approximately 1-2 weeks earlier than those in the ventral pole. This suggests that dorsal neurons may contribute to function sooner. However, the prolonged maturation of new neurons in the ventral hippocampus may provide them with a longer window of time during which they are more plastic and function differently than the mature neuronal population. These findings indicate that neurons born in different hippocampal subregions are subject to different intrinsic maturation clocks or different exposure to activity or other factors regulating neuronal maturation. In addition, they reveal the possibility that different hippocampal behaviors might be affected by suppression of adult neurogenesis with distinct time courses.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
U.S. National Institute of Mental Health
Zip Code
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

Showing the most recent 10 out of 30 publications