Sharma Kaustubh, Govar Armita A, Ghimire Bandana, Nishimori Katsuhiko, Hammock Elizabeth, Teruyama Ryoichi
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
Laboratory of Obesity and Internal Inflammation, Fukushima Medical University, Fukushima, Japan.
J Neuroendocrinol. 2023 Oct;35(10):e13337. doi: 10.1111/jne.13337. Epub 2023 Oct 2.
Maternal care is crucial for the survival and development of offspring. Oxytocin modulates maternal behavior by binding to oxytocin receptors (OXTRs) in various parts of the brain. Previously, we showed that OXTRs are expressed in the anteroventral periventricular nucleus (AVPV) of female, but not male mice. Because the AVPV is involved in the regulation of maternal behavior and oxytocin enhances its induction, this finding leads to the hypothesis that the female specific population of OXTR neurons in the AVPV regulates maternal behavior. To address this hypothesis, OXTR-Venus reporter mice were used to assess if expression levels of OXTR in the AVPV are changed during the postpartum period. The total number of OXTR-Venus neurons was significantly greater in postpartum dams compared to virgin females. To assess efferent projections of the AVPV-OXTR neurons, a Cre-dependent fluorescent protein (tdTomato) expressing a viral vector was injected into one side of the AVPV of female OXTR-Cre mice. Fibers expressing tdTomato were found in hypothalamic areas containing oxytocin neurons (the supraoptic and paraventricular nuclei) and the midbrain areas (the ventral tegmental area and periaqueductal gray) that are involved in the regulation of maternal motivation. To assess if activity of the AVPV-OXTR neurons is involved in the regulation of maternal behaviors, a chemogenetic approach was employed. Specific inhibition of activity of AVPV-OXTR neurons completely abolished pup retrieval and nest building behaviors. Collectively, these findings demonstrate that AVPV-OXTR neurons in postpartum female mice constitute an important node in the neural circuitry that regulates maternal behavior.
母性关怀对于后代的生存和发育至关重要。催产素通过与大脑各部位的催产素受体（OXTRs）结合来调节母性行为。此前，我们发现OXTRs在雌性小鼠而非雄性小鼠的室周前腹侧核（AVPV）中表达。由于AVPV参与母性行为的调节，且催产素可增强其诱导作用，这一发现引发了一个假设，即AVPV中OXTR神经元的雌性特异性群体调节母性行为。为了验证这一假设，使用了OXTR-Venus报告基因小鼠来评估产后期间AVPV中OXTR的表达水平是否发生变化。与未生育的雌性小鼠相比，产后母鼠中OXTR-Venus神经元的总数显著更多。为了评估AVPV-OXTR神经元的传出投射，将一种表达Cre依赖型荧光蛋白（tdTomato）的病毒载体注射到雌性OXTR-Cre小鼠的一侧AVPV中。在含有催产素神经元的下丘脑区域（视上核和室旁核）以及参与母性动机调节的中脑区域（腹侧被盖区和导水管周围灰质）中发现了表达tdTomato的纤维。为了评估AVPV-OXTR神经元的活动是否参与母性行为的调节，采用了化学遗传学方法。对AVPV-OXTR神经元活动的特异性抑制完全消除了幼崽找回和筑巢行为。总的来说，这些发现表明，产后雌性小鼠中的AVPV-OXTR神经元构成了调节母性行为的神经回路中的一个重要节点。
