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 completed a study examining the activation of young neurons in adult mice by spatial learning in novel and familiar environments. Responses in new neurons were compared to those in mature neurons of the same type (granule neurons), hippocampal pyramidal neurons, and anterior cingulated cortical neurons all of which are believed to play a role in spatial learning. In immature granule neurons, prior exposure to many days of spatial water maze training in multiple environments resulted in activation of more neurons. The novelty of the environment on the final day had no effect on young granule cells, arguing against a role for these young neurons in novelty detection. Neurons in the anterior cingulate cortex were very different from young granule cells;they were strongly activated in a novel environment and showed no effect of prior training. Mature granule cells and CA3 pyramidal cells showed mixed responses, with highest activation in animals trained in multiple environments that were exposed to a novel environment on the last day. CA1 pyramidal neurons showed no significant changes in activation across any training condition. In mice exposed to the water maze for the first time, neurons in CA3, CA1 and the anterior cingulate cortex were activated by this highly novel experience, while young granule cells showed decreased neuronal activation in these mice relative to controls that were not put in the water maze. These findings suggest that neurons in the hippocampus proper and anterior cingulated cortex are activated by novel experience. Young granule neurons show a very different pattern of activation by experience than mature granule neurons or other hippocampal and neocortical neurons involved in spatial learning. The young neurons show decreased activation in response to very novel situations and greater activation with a greater variety of prior experience, consistent with inhibition of activation in stressful situations. These findings build on previous work in the lab showing that new neurons are activated primarily in the ventral hippocampus, a region that is important for fear- and anxiety-related behavior, and that loss of new neurons alters stress response and behavior in tests of depressive behavior.

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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
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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