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Effects of adverse early-life environment on the wiring and connectivity of neural circuits involved in the regulation of stress responses during critical periods of development

Objective

An adverse early familial environment, especially disruption of the mother-infant relationship, during critical periods of development can permanently affect stress reactivity (i.e. hypothalamo-pituitary-adrenal (HPA) axis activity) and susceptibility to develop stress-related disorders. During the stress hyporesponsive period (SHRP) (postnatal days (PND) 4-14), rat neonates display low basal and stress-induced corticosterone (CORT) levels in response to mild stressors. A single, 24-hour maternal separation (MS) during the SHRP was shown to cause neonates to prematurely emerge from the SHRP and display elevated basal and stress-induced levels of CORT, characteristics that endure into adulthood.

Although a number of immediate changes in gene expression within specific HPA axis-related areas have been observed in response to MS in early life, little is known about how these alterations might translate or persist into long-lasting effects on stress reactivity in adulthood. We hypothesize that early-life adverse events, and concomitant changes in stress-responsive gene networks, translate into persistent effects via permanent structural alterations in the HPA axis-related neurocircuitry. To address this hypothesis, we propose to examine HPA axis-related areas for evidence of differential wiring and connectivity immediately, and several months following MS.

For this purpose, we combine state-of-the-art tract-tracing, immunohistochemistry, confocal microscopy, and electrophysiological techniques. The results of these experiments will represent one of the first, and more elaborate attempts, to investigate whether and how structural anatomical alterations in stress circuitry may underlie HPA axis dysfunction and susceptibility to develop stress-related disorders in adulthood.

Call for proposal

FP6-2002-MOBILITY-7
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Funding Scheme

IIF - Marie Curie actions-Incoming International Fellowships

Coordinator

UNIVERSITEIT LEIDEN
Address
Einsteinweg 55
Leiden
Netherlands