ESR1 adenoviral particles

Maternal behavior depends on estrogen receptor α (ERα; Esr1) and oxytocin receptor (OTR) signaling in the medial preoptic area (MPOA) of the hypothalamus, as well as dopamine signaling from the ventral tegmental area (VTA) to forebrain regions. Previous studies in rats have shown that low levels of maternal care, especially licking/grooming (LG), lead to reduced levels of MPOA ERα and VTA dopamine neurons in female offspring and predict lower levels of postpartum maternal behavior in these offspring. Here, researchers aimed to determine the functional consequences of neonatal ERα manipulation on behavior in females experiencing low and high levels of postpartum maternal LG. Adenovirus expressing ESR1 was targeted to the MPOA of female pups from low- and high-LG litters on postnatal days 2-3. Overexpression of ESR1 in low-LG offspring increased levels of ERα-immunoreactive cells in the MPOA and tyrosine hydroxylase cells in the VTA to levels observed in high-LG females. Overexpression of ESR1 in juvenile female low-LG offspring also reduced the latency to display maternal behaviors toward donor pups. These results suggest that viral-mediated expression of ESR1 in the neonatal rat hypothalamus results in lasting changes in ESR1 expression during juvenile life and can "rescue" hormone receptor levels and behaviors in offspring raised by low-LG dams, likely mediated by downstream alterations in reward circuits. Thus, the transmission of maternal behavior from one generation to the next can be augmented by neonatal ERα in the MPOA.

TH-ir cells were counted in the nuclei of the VTA and SN in control and Ad-ESR1 females (Figure 1A). Two-way ANOVA indicated that there were significant main effects of maternal LG and virus on TH-ir cells throughout the VTA (Figure 4B). This was primarily driven by differences in the parabranchial pigmented nucleus (PBP) of the VTA, as no significant effects were observed for any other VTA nuclei. A significant interaction between maternal LG and virus was found on TH-ir cells counted in the PBP (Figure 1B). Further analysis indicated that low LG and high LG control animals differed significantly in TH-ir cells in the PBP and throughout the VTA, such that a greater number of TH-ir cells were found in high LG females. In low LG females, more TH-ir cells were found in the PBP of Ad-ESR1 compared to control animals. These differences were not detected in high LG females. There was also a positive linear correlation between ERa-ir cells in the MPOA and TH-ir cells in the PBP (Figure 1D). In the SN, high-LG control females and low-LG females receiving ad-ESR1 had increased TH-ir in the compact dorsal layer of SN-pars compared with low-LG control females. These findings suggest that maternal LG and neonatal ERa have an effect on midbrain dopamine neurons.

Figure 1. TH-ir cells in the ventral midbrain of control and Ad-ESR1 low and high LG offspring. (Peña C J, Champagne F A., 2015)