Hippocampal neural dynamics driving affiliation and attachment

摘要： 依恋有力地塑造了我们的发展，并仍然是健康和幸福的主要驱动力 成年后，依恋的中断是非常痛苦的。虽然从属关系被定义为一般积极的社会 在哺乳动物中广泛共享的相互作用、依恋或作为纽带结果的选择性联系，远远 更罕见，而且与人类有首要的相关性。虽然已经在许多背景下研究了从属关系，但如何 最终影响成人依恋的神经回路在很大程度上仍不为人所知。在……里面 在这个提案中，我们将采取一个比较的框架来了解基本的电路和神经元模式 这是非选择性依恋的基础，最终是参与的，也是成年后选择性依恋的基础。 具体地说，我们将研究小鼠附属行为的神经生物学是如何详细阐述的，以支持 由一夫一妻制的草原田鼠和群居的果蝠形成的更复杂的依恋，代表着 社会关系的光谱。我们将重点关注海马区CA2，因为它已经被证明扮演着一个 在社会行为中的特殊作用，并接受来自催产素和加压素产生细胞的直接输入 脑室旁的下丘脑。具体地说，我们将测试CA2种群的总体假设 在交配前和交配期间，不同物种的活动模式遵循类似的轨迹，随后偏离到 小鼠(Golshani/Hong)的因果驱动关联调查和草原田鼠不同形式的依恋 (唐纳森)和蝙蝠(Yartsev)。为了验证这一假设，我们将改进并使用新一代开源软件 无线微型显微镜(Aharoni)，将允许对大量神经元群体进行长期记录 在行为自由的动物身上。肯尼迪将带来计算专业知识，并允许统一的数据分析 跨物种的框架。在目标1中，我们将在小鼠、草原田鼠和蝙蝠身上进行体内钙成像以进行测试 交配经历调制CA2神经动力学和CA2活动模式编码的假说 空间和身份信息。我们假设，对交配伙伴形成依恋的物种，活动 模式将区分首选合作伙伴和非首选合作伙伴。在目标2中，我们将使用化学发生抑制 CA2在所有物种中的作用，以确定CA2是否因果地驱动附属和依恋行为。在《目标3》中我们 将检验这样的假设，即抑制CA2的加压素输入将降低CA2的维度 交配后的种群活动模式，在所有物种中都会减少对配偶的记忆，在田鼠和蝙蝠中， 降低前一次交配伴侣身份的可识别性。在技术发展目标中，我们将 研制和测试具有远距离充电功能的“真无线”数字数据传输显微镜 能够在没有人工干预的情况下长时间成像。

Abstract: Attachment powerfully shapes our development and remains a primary driver of health and well-being in adulthood; disruption of attachments is highly traumatic. While affiliation, defined as general positive social interactions, is shared widely among mammals, attachment, or selective affiliation as a result of a bond, is far rarer and of primary relevance to humans. While affiliation has been studied in a number of contexts, how the neural circuitry that underlies affiliation ultimately contributes to adult attachment remains largely unknown. In this proposal, we will take a comparative framework to understand how the basic circuitry and neuronal patterns that underlie non-selective affiliation are ultimately engaged and underlie selective attachment in adulthood. Specifically, we will examine how the neurobiology of affiliative behavior in mice has been elaborated to support the more complex attachments formed by monogamous prairie voles and gregarious fruit bats, representing a spectrum of social relationships. We will focus on the hippocampal CA2 region as it has been shown to play a specialized role in social behavior and receives direct inputs from oxytocin and vasopressin producing cells in the paraventricular hypothalamus. Specifically, we will test the overarching hypothesis that CA2 population activity patterns follow similar trajectories across species before and during mating, and subsequently diverge to causally drive affiliative investigation in mice (Golshani/Hong) and different forms of attachment in prairie voles (Donaldson) and bats (Yartsev). To test this hypothesis we will refine and use new generation open-source wireless miniaturized microscopes (Aharoni) that will allow prolonged recordings of large neuronal populations in freely behaving animals. Kennedy will bring computational expertise and allow a unified data analysis framework cross species. In Aim 1 we will perform in-vivo calcium imaging in mice, prairie voles and bats to test the hypothesis that mating experiences modulate CA2 neural dynamics and that CA2 activity patterns encode spatial and identity information. We hypothesize that species that form attachments to mating partners, activity patterns will differentiate preferred vs. non-preferred partners. In Aim 2 we will use chemogenetic inhibition of CA2 in all species to determine whether CA2 causally drives affiliative and attachment behaviors. In Aim 3 we will test the hypothesis that inhibition of vasopressin inputs to CA2 will reduce the dimensionality of CA2 population activity patterns after mating, diminish memory of the mate in all species, and in voles and bats, reduce the decodability of the identity of the previous mating partner. In a technology development aim, we will develop and test a “true wireless” digital data transmitting microscope with power over distance charging capability that will allow prolonged imaging over many hours without human intervention.