OVERALL CENTER ABSTRACT This application is in response to Program Announcement (PA) Number PAR-06-053 Interdisciplinary Developmental Centers for Mental Health (IDSC): Mature Centers (P50). The proposed Center represents a unique marshaling of the talents of a distinguished group of scientists with expertise in cognitive and affective development and systems-level neuroscience, pediatric imaging, molecular biology, mouse models, and biostatistical analysis. We will use an endophenotype approach to examine the impact of brain-derived neurotrophic factor (BDNF) and experiential events (e.g., stress and enrichment) across development on three forms of learning (contextual, cued, extinction) and their associated neural circuitry. Disruption of these learning systems is at the core of many forms of psychiatric disorders, allowing us to examine vulnerability and resistance to psychopathology as a function of stress and genotype. The strength of this proposal is the elegant mapping of human and animal projects, such that transgenic mouse models will provide a constrained interpretation of gene-environment interactions in developing humans. The Center is comprised of 3 highly interdependent projects and 2 cores (Administrative and Data Management Core and Statistical Genetics Cores) designed to provide resources and support for each of the projects. There are three overarching Center aims. First, using both human imaging and animal models, we will track the developmental trajectory of brain systems involved in learning as a function of BDNF genotype (Projects I and III). Second, we will characterize the impact of different forms of stress, including early, severe stress (Projects II and III) and current, mild stress (Project I) on these brain systems during development as a function of BDNF genotype. Third, we will test the extent to which the endophenotypic differences as a function of BDNF genotype can be rescued genetically or environmentally (Project I, II, and III). The proposed studies will collectively test three sets of hypotheses about the role of gene-environment interactions in learning and development in the context of BDNF. These hypotheses include predictions pertaining to: 1) changes in behavioral and neuroanatomical measures of learning as a function of both BDNF genotype and developmental changes in BDNF levels;2) how BDNF genotype modulates the impact adversity on learning and associated circuitry;and 3) rescue of BDNF phenotype through environmental and/or genetic manipulations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH079513-05
Application #
8316384
Study Section
Special Emphasis Panel (ZMH1-ERB-A (05))
Program Officer
Garvey, Marjorie A
Project Start
2008-05-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$1,739,185
Indirect Cost
$699,222
Name
Weill Medical College of Cornell University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Proenca, Catia C; Song, Minseok; Lee, Francis S (2016) Differential effects of BDNF and neurotrophin 4 (NT4) on endocytic sorting of TrkB receptors. J Neurochem 138:397-406
Pitula, Clio E; Wenner, Jennifer A; Gunnar, Megan R et al. (2016) To trust or not to trust: social decision-making in post-institutionalized, internationally adopted youth. Dev Sci :
Zhou, Yan; Huang, Ted; Lee, Francis et al. (2016) Involvement of Endocannabinoids in Alcohol "Binge" Drinking: Studies of Mice with Human Fatty Acid Amide Hydrolase Genetic Variation and After CB1 Receptor Antagonists. Alcohol Clin Exp Res 40:467-73
Lee, T T-Y; Hill, M N; Lee, F S (2016) Developmental regulation of fear learning and anxiety behavior by endocannabinoids. Genes Brain Behav 15:108-24
Pattwell, Siobhan S; Liston, Conor; Jing, Deqiang et al. (2016) Dynamic changes in neural circuitry during adolescence are associated with persistent attenuation of fear memories. Nat Commun 7:11475
Glatt, Charles E; Lee, Francis S (2016) Common Polymorphisms in the Age of Research Domain Criteria (RDoC): Integration and Translation. Biol Psychiatry 79:25-31
Dincheva, Iva; Lynch, Niccola B; Lee, Francis S (2016) The Role of BDNF in the Development of Fear Learning. Depress Anxiety 33:907-916
Johnson, D C; Casey, B J (2015) Easy to remember, difficult to forget: the development of fear regulation. Dev Cogn Neurosci 11:42-55
Song, Minseok; Giza, Joanna; Proenca, Catia C et al. (2015) Slitrk5 Mediates BDNF-Dependent TrkB Receptor Trafficking and Signaling. Dev Cell 33:690-702
Hodel, Amanda S; Hunt, Ruskin H; Cowell, Raquel A et al. (2015) Duration of early adversity and structural brain development in post-institutionalized adolescents. Neuroimage 105:112-9

Showing the most recent 10 out of 64 publications