The broad, long-term objective of this proposal is to gain a better understanding of the function of adult neurogenesis in the hippocampus. The following approaches will be used to achieve this general goal: 1) examination of the impact of socially and spatially complex experiences on new neurons, hormones levels and learning; 2) Exploration of the interaction between sleep, new neurons and learning; 3) determination of the impact of new neuron depletion on hippocampal function; and 4) characterization of differences between mature and immature neurons. Living under standard laboratory conditions has a profound negative impact on the survival of new neurons in the hippocampus. Therefore, a major goal of the experiments proposed is to identify the elements of a naturalistic, relatively complex environment that are important for hippocampal neurogenesis. The production, survival and phenotype of new cells in the hippocampus will be assessed with bromodeoxyuridine (BrdU) labeling combined with immunocytochemistry for cell-type specific markers, hormone levels will be assessed via radioimmunoassay and hippocampal function will be assessed by a variety of associative learning tasks, including trace eyeblink conditioning, trace fear conditioning, context fear conditioning and spatial learning in a Morris water maze. These techniques will be applied to animals that have been exposed to different social experiences, deprived of different stages of sleep or pharmacologically depleted of new neurons. A final series of studies will examine the structural and biochemical characteristics of neurons generated in adulthood compared to those generated during development. These experiments will use neuroanatomical tract tracing combined with BrdU labeling, electron microscopy combined with 3H-thymidine labeling and confocal microscopy. Because stress, sleep and the hippocampus have been linked to several psychiatric conditions, many of which have a cognitive component, these results may elucidate the brain mechanisms that underlie the development of psychopathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH059740-07
Application #
6989109
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Winsky, Lois M
Project Start
1999-05-01
Project End
2007-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
7
Fiscal Year
2006
Total Cost
$334,251
Indirect Cost
Name
Princeton University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Leuner, Benedetta; Caponiti, Julia M; Gould, Elizabeth (2012) Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids. Hippocampus 22:861-8
Leuner, Benedetta; Glasper, Erica R; Gould, Elizabeth (2010) Parenting and plasticity. Trends Neurosci 33:465-73
Leuner, Benedetta; Gould, Elizabeth (2010) Dendritic growth in medial prefrontal cortex and cognitive flexibility are enhanced during the postpartum period. J Neurosci 30:13499-503
Leuner, Benedetta; Gould, Elizabeth (2010) Structural plasticity and hippocampal function. Annu Rev Psychol 61:111-40, C1-3
Leuner, Benedetta; Glasper, Erica R; Gould, Elizabeth (2009) Thymidine analog methods for studies of adult neurogenesis are not equally sensitive. J Comp Neurol 517:123-33
Leuner, Benedetta; Mirescu, Christian; Noiman, Liron et al. (2007) Maternal experience inhibits the production of immature neurons in the hippocampus during the postpartum period through elevations in adrenal steroids. Hippocampus 17:434-42
Stranahan, Alexis M; Khalil, David; Gould, Elizabeth (2007) Running induces widespread structural alterations in the hippocampus and entorhinal cortex. Hippocampus 17:1017-22
Bangasser, Debra A; Waxler, David E; Santollo, Jessica et al. (2006) Trace conditioning and the hippocampus: the importance of contiguity. J Neurosci 26:8702-6
Shors, Tracey J (2006) Significant life events and the shape of memories to come: a hypothesis. Neurobiol Learn Mem 85:103-15
Tanapat, Patima; Hastings, Nicholas B; Gould, Elizabeth (2005) Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose- and time-dependent manner. J Comp Neurol 481:252-65

Showing the most recent 10 out of 18 publications