Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

Abstract

During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF 1 ) by systemic antalarmin administration (20 mg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF 1 in modulating early-life stress-induced prefrontal abnormalities.

Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease

“…In basal dendrites of the infralimbic mPFC neurons, we demonstrated a reduction in dendritic complexity both after ELS and EH. In line with our findings, the ELS paradigm reduced the dendritic complexity of the mPFC [63], although very little is known about effects of EH on dendritic morphology in the mPFC. In AD patients, activity in the mPFC is increased, possibly as a compensation for the decline in cognitive capacity in other brain areas [64].…”

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

“…After chronic early-life stress in rodents, impoverished dendritic trees and reduced hippocampal volume have been described ( 2015b), and similar dendritic changes were found in the prefrontal cortex (Radley et al, 2008;Yang et al, 2015). In humans, chronic early-life stress such as rearing in orphanages promotes reduced volume of the cortex (especially prefrontal) as well as hippocampus and the latter correlates with stress duration (Hodel et al, 2015).…”

Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex?

“…Studies assessing the effects of stress during the first weeks of life in rodents indicate that maternal separation or other disruptions to the early environment change neuronal morphology of the frontal cortex (Brenhouse et al, 2013; Bock et al, 2005; Chocyk et al, 2013; Monroy et al, 2010; Muhammad and Kolb, 2011; Yang et al, 2015). These structural changes are accompanied by changes to cognition supported by frontal circuits (Lovic and Fleming, 2004; Thomas et al, 2015; Yang et al, 2015).…”