This proposal for a NIH Pathway to Independence Award (ROO component) aims to elucidate neurodevelopmental underpinnings of emotional dysregulation which may play a role in the onset of anxiety and mood disorders. Innate differences in personality and emotional reactivity strongly shape how individuals respond to stress, and this biological endowment together with early-life experience can powerfully influence neural and emotional development. Understanding the neurobiological mechanisms whereby inborn and environmental factors interact to contribute to the onset of affective dysfunction in the developing brain is crucial for generating improved preventative treatments. Thus, the proposed studies use a novel animal model of depression and anxiety to elucidate the ontogeny of emotional neural circuits to better understand how altered wiring during development may give rise to emotional dysfunction later in life. Preliminary work revealed that anxiety- and depression-prone Low Novelty Reactive (LR) rats exhibit marked differences in the developing hippocampus compared to High Novelty Reactive (HR) animals.
The Specific Aims of this project are examining: 1) the ontogeny of hippocampal circuits in baseline LR versus HR animals;2) how their behavior and underlying neural circuits are modulated by environmental factors such as maternal care; and 3) how early life manipulation of hippocampal circuitry (via exposure to the growth factor FGF2) impacts brain development and later emotional behavior. The overarching goal of the proposed research is to identify neurodevelopmental mechanisms that may underlie key aspects of individual differences in emotionality and susceptibility to depression and anxiety.

Public Health Relevance

Inborn differences in personality and temperament strongly influence how individuals respond to stress and put some people at risk for developing emotional disorders such as depression and anxiety. This proposal uses an animal model of depression/anxiety to study how abnormal brain development may give rise to emotional dysfunction later in life. Ultimately this work hopes to improve our understanding of the neurobiology of emotional disorders and help to develop improved treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Transition Award (R00)
Project #
4R00MH085859-02
Application #
8203130
Study Section
Special Emphasis Panel (NSS)
Program Officer
Panchision, David M
Project Start
2011-03-15
Project End
2014-02-28
Budget Start
2011-03-15
Budget End
2012-02-29
Support Year
2
Fiscal Year
2011
Total Cost
$231,167
Indirect Cost
Name
University of Alabama Birmingham
Department
Psychiatry
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
McCoy, Chelsea R; Rana, Samir; Stringfellow, Sara Anne et al. (2016) Neonatal maternal separation stress elicits lasting DNA methylation changes in the hippocampus of stress-reactive Wistar Kyoto rats. Eur J Neurosci 44:2829-2845
McCoy, Chelsea R; Golf, Samantha R; Melendez-Ferro, Miguel et al. (2016) Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior. Neuroscience 324:469-484
Rana, Samir; Nam, Hyungwoo; Glover, Matthew E et al. (2016) Protective effects of chronic mild stress during adolescence in the low-novelty responder rat. Stress 19:133-8
Glover, M E; Pugh, P C; Jackson, N L et al. (2015) Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats. Neuroscience 284:775-97
Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C et al. (2015) Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety. Dev Neurosci 37:203-14
Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C et al. (2015) Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety. Dev Neurosci 37:203-14
Rana, Samir; Pugh, Phyllis C; Jackson, Nateka et al. (2015) Inborn stress reactivity shapes adult behavioral consequences of early-life maternal separation stress. Neurosci Lett 584:146-50
Clinton, Sarah M; Watson, Stanley J; Akil, Huda (2014) High novelty-seeking rats are resilient to negative physiological effects of the early life stress. Stress 17:97-107
Simmons, Rebecca K; Stringfellow, Sara A; Glover, Matthew E et al. (2013) DNA methylation markers in the postnatal developing rat brain. Brain Res 1533:26-36
Cummings, Jennifer A; Clinton, Sarah M; Perry, Adam N et al. (2013) Male rats that differ in novelty exploration demonstrate distinct patterns of sexual behavior. Behav Neurosci 127:47-58

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