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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