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.

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Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2013
Total Cost
$1,549,402
Indirect Cost
Name
U.S. National Institute of Mental Health
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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:
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
Snyder, Jason S; Grigereit, Laura; Russo, Alexandra et al. (2016) A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis. eNeuro 3:
Inta, Dragos; Cameron, Heather A; Gass, Peter (2015) New neurons in the adult striatum: from rodents to humans. Trends Neurosci 38:517-23
Smart, DeeDee; Garcia-Glaessner, Alejandra; Palmieri, Diane et al. (2015) Analysis of radiation therapy in a model of triple-negative breast cancer brain metastasis. Clin Exp Metastasis 32:717-27
Cameron, Heather A; Glover, Lucas R (2015) Adult neurogenesis: beyond learning and memory. Annu Rev Psychol 66:53-81
Pelkey, Kenneth A; Barksdale, Elizabeth; Craig, Michael T et al. (2015) Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons. Neuron 85:1257-72
Schoenfeld, Timothy J; Cameron, Heather A (2015) Adult neurogenesis and mental illness. Neuropsychopharmacology 40:113-28
Kuipers, Sjoukje D; Bramham, Clive R; Cameron, Heather A et al. (2014) Environmental control of adult neurogenesis: from hippocampal homeostasis to behavior and disease. Neural Plast 2014:808643

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