Developmental process are activated and shaped by stimulation. Sources of stimulation or experience can be found within the developing organism's habitat. The transition from fetus to newborn infant, heralded by labor and birth, is characterized by a multitude of neural, physiological and behavioral changes that assist successful acclimation to the extrauterine world. The proposed studies focus on intrauterine determinants of neural and behavioral development in relation to labor contractions, the catecholamine system, adult phenotypes and their causal relations. The Norway rat will be used in psychobiological investigations spanning behavioral, physiological, neural and molecular levels of analysis. Intrauterine chemosensory experience, labor contractions, and suckling onset at birth will be analyzed in biobehavioral studies of perinatal learning. Specific effects of labor, i.e., somatosensory stimulation and intermittent hypoxia, will be studied and related to birth complications. Birth-related activation of norepinephrine (NE), dopamine (DA), will be analyzed using pharmacological agents. Neural upregulation of c-fos will be used to guide brain localization studies involving key players in catecholamine systems. To identify relations between intrauterine experience and later developmental phases, adult phenotypes and their emergence will be analyzed. Our framework recognizes the mammalian mother as a pathway for inducing, canalizing, and regulating developmental change. Some studies will analyze whether dams respond differently to pups with different intrauterine experiences. This research program has broad and significant implications for numerous biomedical concerns, including premature birth, birth complications, and stress, psychiatric and pathophysiological disorders, including schizophrenia, substance abuse, attention deficit hyperactivity disorder (ADHD), and Tourette's Syndrome (TS).

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD050201-15
Application #
7849021
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Freund, Lisa S
Project Start
1990-06-15
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
15
Fiscal Year
2010
Total Cost
$272,649
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn et al. (2017) Intrauterine exposure to maternal stress alters Bdnf IV DNA methylation and telomere length in the brain of adult rat offspring. Int J Dev Neurosci 62:56-62
Kleven, Gale A; Booth, Heather M; Voogd, Marco et al. (2014) L-dopa reverses behavioral deficits in the Pitx3 mouse fetus. Behav Neurosci 128:749-59
Morgan, Jonathan J; Kleven, Gale A; Tulbert, Christina D et al. (2013) Longitudinal 1H MRS of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development. NMR Biomed 26:683-91
Kleven, Gale A; Joshi, Priyanka; Voogd, Marco et al. (2013) Prenatal ontogeny of the dopamine-dependent neurobehavioral phenotype in Pitx3-deficient mice. Eur J Neurosci 37:1564-72
Kleven, Gale A; Ronca, April E (2009) Prenatal behavior of the C57BL/6J mouse: a promising model for human fetal movement during early to mid-gestation. Dev Psychobiol 51:84-94
Casey, Theresa; Patel, Osman; Dykema, Karl et al. (2009) Molecular signatures reveal circadian clocks may orchestrate the homeorhetic response to lactation. PLoS One 4:e7395
Ronca, April E; Fritzsch, Bernd; Bruce, Laura L et al. (2008) Orbital spaceflight during pregnancy shapes function of mammalian vestibular system. Behav Neurosci 122:224-32
Ronca, April E; Abel, Regina A; Alberts, Jeffrey R (2007) Maternal anesthesia via isoflurane or ether differentially affects pre-and postnatal behavior in rat offspring. Dev Psychobiol 49:675-84
Ronca, April E; Abel, Regina A; Ronan, Patrick J et al. (2006) Effects of labor contractions on catecholamine release and breathing frequency in newborn rats. Behav Neurosci 120:1308-14