Anatomical and functional characterization of fear-activated oxytocin neurons

催产素（Oxytocin，OXT）是一种进化上古老的下丘脑神经肽，在哺乳动物分娩和泌乳的神经内分泌调控中起着重要作用。除了这些效果，OXT还能协调各种类型的社会行为，增强信任，减轻恐惧。最近，应用细胞类型特异性靶向的OXT神经元的重组腺相关病毒（rAAV），我们表明，OXT释放的长距离轴突在中央杏仁核抑制恐惧条件大鼠的冻结行为。这一发现提出了一个关于内源性OXT释放如何在恐惧时协调的问题。我们解决这个问题，在这个项目中，采用rAAV表达荧光标记或通道视紫红质2在这些OXT神经元，开始表达c-fos的反应恐惧。在这项研究中，我们将追求两个目标：（1）研究-通过使用重组病毒-“恐惧敏感”（即。e. c fos表达）的OXT神经元与中央杏仁核和控制恐惧反应的其他前脑结构; 2）通过在体外和体内采用组合的病毒和光遗传学方法来研究“恐惧敏感”OXT神经元的功能意义。此外，该组合将进一步与微透析技术一起应用于探测蓝光诱发的OXT从轴突终末的局部释放。

Oxytocin (OXT) is an evolutionarily ancient hypothalamic neuropeptide, which plays a crucial role in the neuroendocrine control of parturition and lactation in mammals. Beside these effects, OXT orchestrates various types of social behaviors, enhancing trust and attenuating fear. Recently, applying cell-type specific targeting of OXT neurons by recombinant adeno-associated virus (rAAV), we showed that OXT release from long-range axons in the central nucleus of amygdala suppresses freezing behavior in fear-conditioned rats. This finding raised a question on how endogenous OXT release is coordinated upon fear. We address this question in this project by employing rAAVs to express fluorescent markers or channel rhodopsin 2 in those OXT neurons, which start to express c-fos in response to fear. In the study we will pursue two goals: (1) To study – by employing recombinant viruses – the anatomical connections of “fear-sensitive” (i. e. cfos expressing) OXT neurons with the central amygdala and other forebrain structures controlling the fear response; 2) To study the functional significance of “fear-sensitive” OXT neurons by employing combined viral and optogenetic approaches in vitro and in vivo. In addition, this combination will be further applied together with the microdialysis technique to probe the bluelight evoked local release of OXT from axonal terminals in vivo.