Physiological identification and characterization of PVN neuronal populations

项目总结(项目2合作伙伴：Buzsaki、Froemke、Lin、Tsien) 我们建议的首要目标是了解催产素信号是如何使大脑系统参与支持 社会空间行为。一个中心问题是下丘脑神经元释放的催产素如何影响神经元 靶结构中的活动，反之，这些协调神经元是如何嵌入和控制的 其他神经元回路。为了实现这一目标，项目2的目标是量化催产素的激发模式- 生理条件下下丘脑室旁核神经元的释放及其与状态依赖放电模式的关系 在伴侣结构中，特别是海马体中。这些实验是以我们的总体假设为指导的 大脑结构涉及母体行为的各个方面，包括幼崽取回和 防御/攻击机制，形成一个包括PVN和VMH核的交互系统 下丘脑。 项目2的第一个任务是找出获得催产素生理特征的方法- 产生PVN神经元。这将通过收集大量波形、射速动态、 神经元相互作用等指标对各种下丘脑室旁核神经元的分类进行了验证， 局部化光源光生法。根据这一目标获得标准将用于以后的工作 用于鉴定催产素神经元的实验。下一个目标是建立大规模和高弹性的长期 来自同一组神经元的录音，用于重复的社会互动，包括暴力攻击。我们 要知道，催产素-下丘脑室旁核神经元也会释放快速的神经递质。因此，一个重要的目标将是 不仅描述了他们的社会互动(项目1和4)，而且还描述了他们在不同大脑状态下的放电模式 以及与种群模式的关系，例如海马体。这些生理测量将是 纤维光度法补充测量不同时间下丘脑室旁核催产素神经元总钙信号 行为状态。相反，我们将扩展相关方法与光遗传诱导的合成 检查PVN和VMH神经元是否以及如何能够 受直接或间接(海马体-外侧隔)通路的影响。

Project Summary (Project 2 Co-PIs: Buzsaki, Froemke, Lin, Tsien) The overarching goal of our proposal is to understand how oxytocin signaling engages brain systems to support socio-spatial behavior. A central question is how oxytocin release from hypothalamic neurons affects neuronal activity in target structures and conversely, how these coordinating neurons are embedded and controlled by other neuronal circuits. Toward this goal, the aims of Project 2 is to quantify the firing patterns of oxytocin- releasing PVN neurons under physiological conditions and their relationship with state-dependent firing patterns in partner structures, particularly the hippocampus. These experiments are guided by our overall hypothesis that brain structures involved in various aspects of a maternal behavior, including pup retrieval and defensive/aggressive mechanisms, form an interactive system that includes the PVN and VMH nuclei of the hypothalamus. The first task of Project 2 is it to would out methods to obtain physiological signatures of oxytocin- producing PVN neurons. This will be accomplished by collecting large number of waveform, firing rate dynamics, neuronal interaction and other criteria of the various PVN neurons and verify the classification with a novel, localized light-source optogenetic method. The criteria obtain under this aim will be used in subsequent experiments to identify oxytocin neurons. The next goal is to establish large-scale and highly resilient long-term recordings from the same sets of neurons for repeated social interactions, including violent attacks. We recognize that oxytocin-PVN neurons also release fast neurotransmitters. Therefore, an important goal will be to characterized their firing patterns not only social interactions (Projects 1 and 4) but also in various brain states and in relationship to population patterns, such as the hippocampus. These physiological measurements will be complemented by fiber photometry to measure the overall Ca2+ signal of PVN oxytocin neurons during different behavioral states. Conversely, we will extend the correlational methods with optogenetic induction of synthetic physiological patterns (`ripples') in the hippocampus to examine whether and how PVN and VMH neurons can be influenced by direct or indirect (hippocampus-lateral septum) pathways.