Local CRF and oxytocin receptors correlate with female experience-driven avoidance change and hippocampal neuronal plasticity.

Understanding how experiences affect females' behaviors and neuronal plasticity is essential for uncovering the mechanism of neurodevelopmental disorders. The study explored how neonatal maternal deprivation (MD) and post-weaning environmental enrichment (EE) impacted the CA1 and DG's neuronal plasticity in the dorsal hippocampus, and its relationships with passive avoidance, local corticotrophin-releasing factor (CRF) levels, and oxytocin receptor (OTR) levels in female BALB/c mice. The results showed that MD damaged passive avoidance induced by foot shock and hotness, and EE restored it partially. In the CA1, MD raised CRF levels and OTR levels. Parallelly, MD increased synaptic connection levels but reduced the branches' numbers of pyramidal neurons. Meanwhile, in the DG, MD increased OTR levels but lowered CRF levels, DNA levels, and spine densities. EE did not change the CA1 and DG's CRF and OTR levels. However, EE added DG's dendrites of granular cells. The additive of MD and EE raised CA1's synaptophysin and DG's postsynaptic density protein-95 and OTR levels, and meanwhile, shaped avoidance behaviors primarily similar to the control. The results suggest that experience-driven avoidance change and hippocampal neuronal plasticity are associated with local CRF and OTR levels in female mice.

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.

Effects of maternal deprivation and environmental enrichment on anxiety-like and depression-like behaviors correlate with oxytocin system and CRH level in the medial-lateral habenula.

The medial-lateral habenula (LHbM)'s role in anxiety and depression behaviors in female mice remains unclear. Here, we used neonatal maternal deprivation (MD) and post-weaning environmental enrichment (EE) to treat female BALB/c offspring and checked anxiety-like and depression-like behaviors as well as the corticotropin-releasing hormone (CRH), oxytocin receptor (OTR), estrogen receptor-beta (ERß) levels in their LHbM at adulthood. We found that MD enhanced state anxiety-like behaviors in the elevated plus-maze test, and EE caused trait anxiety-like behaviors in the open field test and depression-like behaviors in the tail suspension test. The immunochemistry showed that MD reduced OT immunoreactive neuron numbers in the hypothalamic paraventricular nucleus but increased OTR levels in the LHbM; EE increased CRH levels in the LHbM but decreased OTR levels in the LHbM. The additive effects of EE and MD maintained the behavioral parameters, OT-ir neuronal numbers, CRH levels, and OTR levels similar to the additive of non-MD and non-EE. The correlation analysis showed that CRH levels correlated with synaptic connection levels, OTR levels correlated with nucleus densities, and ERß levels correlated with Nissl body levels and body weights in female mice. Neither MD nor EE affected ERß levels in the LHbM. Together, the study revealed the relationships between behaviors and neuroendocrine and neuronal alterations in female LHbM and the effects of experiences including MD and EE on them.