Experiences Shape Hippocampal Neuron Morphology and the Local Levels of CRHR1 and OTR.

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1's OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1's and CA2's CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3's CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1's neuronal branches and the CA2's and DG's synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

Oxytocin system driven by experiences modifies social recognition and neuron morphology in female BALB/c mice.

The oxytocin (OT) system, affected by life experiences, modulates neuron morphology in a sex-specific manner, leading to sex differences in social interactions. To date, few studies have focused on the OT system and social interactions of female mice. In this study, we used maternal deprivation (MD) and its possible treatment, environmental enrichment (EE), to affect social recognition in female BALB/c mice. We checked neuron morphology, synaptic connections, oxytocinergic (OTergic) neurons in the hypothalamus paraventricular nucleus (PVH), and OT receptor (OTR) in the basolateral amygdala (BLA) and layer II/III of the prelimbic cortex (PL). Our results showed that MD induced social recognition impairments, increased OTR levels in the BLA, and, meanwhile, reduced OTergic neurons in the magnocellular region of the PVH (mPVH). Decreased Nissl bodies, increased cell nuclei, and increased dendrites of projection neurons paralleled the increased OTR levels in the BLA of MD mice. EE restored MD-induced the impairments of novel object recognition and sociability; this effect paralleled a decrease in cell density in the PL and an increase in OTergic neurons in the parvocellular regions of the PVH and synaptic connections in the BLA and layer II/III of the PL. Our findings indicate that early life stress such as MD impairs social recognition, and meanwhile, remodels neuron morphology region-specifically in the female brain, apparently in the BLA but slightly in the PL; and EE could partially restore the deficits induced by MD. The results provide new insights into sex differences in the prevalence of psychological development disorders.

Experiences affect social behaviors via altering neuronal morphology and oxytocin system.

Life experiences, such as maternal deprivation (MD) and environment enrichment (EE), affect social behaviors in the adult. But, the underlying mechanism remains unclear. In the present study, we determined whether neonatal MD induces social deficits, whether postweaning EE restores the deficits, and their effects on neuron morphology and oxytocin (OT)-oxytocin receptor (OTR) system. We found that MD induced repetitive behavior and deficits in novel object recognition and sociability, and EE alleviated these deficits. MD decreased oxytocinergic neurons in the magnocellular hypothalamic paraventricular nucleus (mPVH), which was parallel to the increased OTR levels and dendritic branches of projection neurons in the basolateral amygdala (BLA). EE increased the OTR levels in the prelimbic cortex (PL) and the oxytocinergic neurons in the parvocellular PVH (vPVH), which were parallel to the increased dendritic branches of small pyramidal neurons in the PL and synaptic connections marked with synaptophysin and postsynaptic density protein 95 in the BLA and PL. Together, the results suggest that postweaning EE alleviates the social impairments induced by neonatal MD and OT-OTR system are experience-dependent and associated with social behaviors and neuron morphology.