Anatomical and functional characterization of fear-activated oxytocin neurons

催产素（OXT）是一种进化古老的下丘脑神经肽，在哺乳动物分娩和哺乳的神经内分泌控制中起着至关重要的作用。除了这些影响外，OXT还协调了各种类型的社会行为，增强了信任，减弱了恐惧。最近，我们利用重组腺相关病毒（rAAV）对OXT神经元进行细胞型特异性靶向，发现杏仁核中央远端轴突释放OXT可抑制恐惧条件下大鼠的冻结行为。这一发现提出了一个问题，即内源性OXT释放是如何在恐惧时协调的。在这个项目中，我们通过使用raav在OXT神经元中表达荧光标记物或通道视紫红质2来解决这个问题，OXT神经元在恐惧反应中开始表达c-fos。在这项研究中，我们将追求两个目标：(1)利用重组病毒研究“恐惧敏感”（即表达cfo）的OXT神经元与中央杏仁核和其他控制恐惧反应的前脑结构的解剖学联系；2)采用病毒与光遗传学相结合的方法，在体外和体内研究“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，以探测蓝光引起的体内轴突末端OXT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.