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。 成年期;附件的中断是高度创伤性的。虽然从属关系，定义为一般积极的社会 相互作用，在哺乳动物中广泛存在，依恋，或作为纽带的选择性联系， 更为罕见，主要与人类有关。虽然在许多情况下研究了从属关系， 最终导致成人依恋的神经回路在很大程度上仍然未知。在 这个建议，我们将采取一个比较框架，以了解如何基本电路和神经元模式， 在成年期，非选择性依恋的基础最终会参与并成为选择性依恋的基础。 具体来说，我们将研究如何在小鼠的亲和行为的神经生物学已经阐述，以支持 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关系，代表了一种 社会关系的范围。我们将重点放在海马CA 2区，因为它已被证明发挥作用， 在社会行为中的专门角色，并从催产素和血管加压素产生细胞中接受直接输入， 室旁下丘脑具体来说，我们将测试总体假设，即CA 2群体 在交配前和交配期间，不同物种的活动模式遵循相似的轨迹，随后出现分歧， 在小鼠中进行因果驱动的依恋调查（Golshani/Hong）和在草原田鼠中进行不同形式的依恋 （唐纳森）和蝙蝠（亚尔采夫）。为了验证这一假设，我们将改进和使用新一代开源 无线微型显微镜（Aharoni），将允许大的神经元群体的长时间记录 行为自由的动物。肯尼迪将带来计算专业知识，并允许统一的数据分析 框架跨物种。在目标1中，我们将在小鼠、草原田鼠和蝙蝠中进行体内钙成像， 假设交配经验调节CA 2神经动力学和CA 2活动模式编码 空间和身份信息。我们假设，物种形成依恋交配伙伴，活动 模式将区分首选与非首选合作伙伴。在目标2中，我们将使用以下化学发生抑制： 所有物种中的CA 2，以确定CA 2是否因果驱动亲和和依恋行为。在目标3中， 将检验抑制加压素输入到CA 2将降低CA 2的维度的假设 交配后的种群活动模式，减少了所有物种对配偶的记忆，在田鼠和蝙蝠中， 降低了先前交配伴侣身份的可解码性。在技术发展目标中，我们将 开发和测试一种“真正的无线”数字数据传输显微镜，具有远距离充电功能 这将允许在没有人为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.