Oxytocin modulation of a distributed neural circuit for maternal behavior

项目总结(项目1，共同绩效指标：Froemke，Lin，Buzsaki) 催产素是一种对社会行为很重要的神经肽，比如母爱和夫妻关系。现在是时候了 认为轴突催产素直接释放到各种前脑靶点对社会行为至关重要，但它 仍不清楚何时何地需要催产素调节来增强社会信息处理和 规范母性行为。催产素对护理是必不可少的，但尚不清楚产妇的其他哪些方面 母亲或无关的共同照料的动物的行为取决于催产素系统。催产素给药 可能在临床上也很有希望，可以改善自闭症谱系障碍、社交焦虑和后抑郁的结果。 产后抑郁症。然而，了解功能解剖和全脑神经是非常必要的。 催产素影响行为变化的回路，包括催产素何时释放，以及是否 后叶催产素的调节方式因性别或社会背景而异。 在这里，我们将解决这一关键的知识差距。最近，我们研制出了第一批特异性抗体 小鼠催产素受体使用这些抗体来确定这些受体的定位，并 研究了催产素如何能够使母鼠的幼崽取回行为。这些先前的研究提供了一种 为当前项目奠定了坚实的基础，在该项目中，我们的团队旨在了解哪些目标神经回路 是否存在可能对催产素调节敏感的行为事件 短暂的社会互动阶段。中心假设是催产素是启动 母亲在关键区域的行为，包括听觉皮质和海马体，但在 经验丰富的母亲。我们将在成年小鼠身上进行行为、光遗传学和电路映射研究，以 确定催产素何时何地调节神经回路，以增强社会信息处理和 随之而来的是改善产妇行为。在目标1中，我们将构建一个新的行为记录系统来 持续监控几天到几周的社交互动。在目标2中，我们分析了催产素投射和催产素 受体在整个成人大脑中的表达，寻找潜在的调制热点。《终极目标3》 和4，我们进行光遗传功能损失和功能增益型实验，以确定在哪里和 何时需要对母亲的行为进行催产素调节，或者在什么时候可能会额外释放催产素 加速母亲行为的开始或改善稳定状态下的表现。 总而言之，我们将在这里研究社会互动和母性行为的出现 在多只动物共居期间自然表达，使用了我们将建立的新的行为监测系统。 然后，我们将使用该系统来确定何时何地需要进行催产素调节以及最有效 在促进亲社会互动和儿童保育方面。

Project Summary (Project 1, Co-PIs: Froemke, Lin, Buzsaki) Oxytocin is a neuropeptide important for social behavior, such as maternal care and pair bonding. It is now believed that direct axonal oxytocin release into various forebrain targets is critical for social behavior, but it remains unclear where and when oxytocin modulation is required to enhance social information processing and regulate maternal behavior. Oxytocin is essential for nursing, but it is unclear what other aspects of maternal behavior by mothers or unrelated co-caring animals depend on the oxytocin system. Oxytocin administration might also be clinically promising, improving outcomes in autism spectrum disorders, social anxiety, and post- partum depression. However, it is imperative to understand the functional anatomy and whole-brain neural circuitry by which oxytocin affects behavioral changes, including when oxytocin might be released, and whether there are differences in oxytocin modulation that depend on gender or social context. Here we will address this critical knowledge gap. Recently, we generated the first specific antibodies to the mouse oxytocin receptor, used these antibodies to determine where these receptors are localized, and examined how oxytocin can enable pup retrieval behavior in maternal mice. Those previous studies provide a robust foundation for the current Project, in which our team aims to understand which target neural circuits are modulated by oxytocin, and if there are behavioral episodes that might be sensitive to oxytocin modulation during brief periods of social interaction. The central hypothesis is that oxytocin is absolutely necessary to initiate maternal behaviors in key areas including auditory cortex and hippocampus, but may be dispensable in experienced mothers. We will perform behavioral, optogenetic, and circuit mapping studies in adult mice to determine where and when oxytocin modulates neural circuits to enhance social information processing and subsequently improve maternal behavior. In Aim 1 we will build a new behavioral recording system to continuously monitor social interactions for days to weeks. In Aim 2, we profile oxytocin projections and oxytocin receptor expression throughout the entire adult brain to find potential hotspots of modulation. Finally in Aims 3 and 4, we perform optogenetic loss-of-function and gain-of-function type experiments to determine where and when oxytocin modulation is needed for maternal behavior or at what points might additional oxytocin release accelerate maternal behavior onset or improve steady-state performance. In summary, here we will study the emergence of social interactions and maternal behaviors as they are naturally expressed during multiple animal co-housing, using a new behavioral monitoring systems we will build. We will then use this system to determine when and where oxytocin modulation is required and most effective at promoting pro-social interactions and child care.