Differential impact of two paradigms of early-life adversity on behavioural responses to social defeat in young adult rats and morphology of CA3 pyramidal neurons

Abstract

Early life stress (ELS) is an important factor in programing the brain for future response to stress, and resilience or vulnerability to stress-induced emotional disorders. The hippocampal formation, with essential roles in both regulating the stress circuitry and emotionality, contributes to this adaptive programing. Here, we examined the effects of early handling (EH) and maternal deprivation (MD) as mild and intense postnatal stressors, respectively, on the behavioural responses to social defeat stress in young adulthood. We also evaluated the interaction of mild and intense ELS with later social defeat (SD) stress on the morphology and dendritic spine density of Golgi-cox-stained CA3 hippocampal neurons. SD stress in adult rats, as expected, increased anxiety and depressive-like behaviours in the open field, elevated plus-maze and forced swimming test. These effects were associated with reduction of dendritic spines and soma size of CA3 neurons. Both behavioural and structural alterations were significantly ameliorated in socially defeated rats that experienced early handling (EH-SD). Basal dendrites of CA3 neurons in EH-SD rats also showed longer dendrites and more intersections with Sholl circles in the distal portion, compared to both control and SD rats. On the other hand, in socially defeated rats with maternal deprivation experience (MD-SD) the stress-induced behavioural and structural alterations were generally intensified compared to SD rats. In MD-SD rats, apical dendrites of CA3 neurons demonstrated remarkable retraction; an effect that was not detected in SD rats. The reduction of dendritic spines density on the apical dendrites of CA3 neurons was also more pronounced in MD-SD rats compared to SD rats. Dendritic arbors and spines comprise the major neuronal substrate for the circuit connectivity, and cell region-specific alterations of dendrites and spines in CA3 neurons reveal plausible mechanisms that can underlie the impact of different ELSs on risk for affective disorders in response to social stress in adulthood.