Abstract：
Birth stress is a risk factor for psychiatric disorders and associated with exaggerated release of the stress hormone arginine vasopressin (AVP) into circulation and in the brain. In perinatal hippocampus, AVP activates GABAergic interneurons which leads to suppression of spontaneous network events and suggests a protective function of AVP on cortical networks during birth. However, the role of AVP in developing subcortical networks is not known. Here we tested the effect of AVP on the dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT, serotonin) system in male and female neonatal rats, since early 5-HT homeostasis is critical for the development of cortical brain regions and emotional behaviors. We show that AVP is strongly excitatory in neonatal DRN: it increases excitatory synaptic inputs of 5-HT neurons via V1A receptors in vitro and promotes their action potential firing through a combination of its effect on glutamatergic synaptic transmission and a direct effect on the excitability of these neurons. Furthermore, we identified two major firing patterns of neonatal 5-HT neurons in vivo, tonic regular firing and low frequency oscillations of regular spike trains and confirmed that these neurons are also activated by AVP in vivo. Finally, we show that the sparse vasopressinergic innervation in neonatal DRN originates exclusively from cell groups in medial amygdala and bed nucleus of stria terminalis. Hyperactivation of the neonatal 5-HT system by AVP during birth stress may impact its own functional development and affect the maturation of cortical target regions, which may increase the risk for psychiatric conditions later on.
摘要：
出生压力是精神疾病的危险因素，与压力激素精氨酸加压素（AVP）过度释放到循环和大脑中有关。在围产期海马中，AVP激活GABA能中间神经元，导致自发网络事件的抑制，并表明AVP在出生期间对皮质网络的保护功能。然而,AVP在皮层下网络发育中的作用尚不清楚.在这里，我们测试了AVP对背中缝核（DRN）5-羟色胺（5-HT，雄性和雌性新生大鼠的血清素）系统，因为早期5-HT稳态对于大脑皮层区域的发育和情绪行为至关重要。我们表明AVP在新生儿DRN中具有强烈的兴奋性：它在体外通过V1A受体增加了5-HT神经元的兴奋性突触输入，并通过其对谷氨酸能突触传递的影响和对兴奋性的直接影响来促进其动作电位放电这些神经元。此外，我们确定了新生儿体内5-HT神经元的两种主要放电模式，补品规则放电和规则尖峰序列的低频振荡，并证实这些神经元在体内也被AVP激活。最后,我们表明，新生儿DRN中稀疏的血管加压素能神经支配仅起源于杏仁核内侧和终末纹床核的细胞群。出生应激期间AVP对新生儿5-HT系统的过度激活可能会影响其自身功能发育并影响皮质靶区的成熟。这可能会增加以后患精神疾病的风险。
