Hippocampal neural dynamics driving affiliation and attachment

海马神经动力学驱动归属和依恋

• 批准号: 10225059
• 负责人: Zoe Rebecca Donaldson
• 金额: $ 482.81万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225059
• 关键词: Adult; Animals; Architecture; Automobile Driving; Behavior; Behavioral; Brain region; Cells; Charge; Chiroptera; Complex; Data; Data Analyses; Development; Dimensions; Disease; Ecosystem; Environment; Fruit; Future; Generations; Health; Hippocampus (Brain); Hour; Human; Hypothalamic structure; Image; Imaging Device; Intervention; Investigation; Mammals; Memory; Methodology; Microscope; Microtus; Mus; Neurobiology; Neurons; Oxytocin; Partner in relationship; Pathway interactions; Pattern; Personal Satisfaction; Play; Population; Role; Sensory; Shapes; Smell Perception; Social Behavior; Social Environment; Social Interaction; Social support; System; Techniques; Technology; Testing; Time; Vasopressins; Wireless Technology; affiliative behavior; comparative; data exchange; design; digital; dyadic interaction; experience; in vivo calcium imaging; insight; miniaturize; movie; neural circuit; neuronal patterning; open source; prairie vole; relating to nervous system; social; social attachment; social relationships; technology development; tool

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.

抽象的： 依恋有力地塑造了我们的发展，并且仍然是健康和福祉的主要驱动力 成年期；依恋关系的破坏是非常痛苦的。而归属感被定义为一般积极的社会关系 相互作用，在哺乳动物之间广泛共享，由于联系而产生的依恋或选择性归属，远非如此 较为罕见且与人类主要相关。虽然从属关系已经在多种背景下进行了研究，但 归属感最终促成成人依恋的神经回路仍然很大程度上未知。在 在这个建议中，我们将采取一个比较框架来理解基本电路和神经元模式是如何 非选择性依恋的基础最终会成为成年后选择性依恋的基础。 具体来说，我们将研究如何详细阐述小鼠亲和行为的神经生物学来支持 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关系，代表了 社会关系的范围。我们将重点关注海马 CA2 区域，因为它已被证明发挥着重要作用 在社会行为中发挥专门作用，并接受来自催产素和加压素产生细胞的直接输入 室旁下丘脑。具体来说，我们将检验 CA2 群体的总体假设 不同物种在交配前和交配过程中的活动模式遵循相似的轨迹，随后出现分歧 因果驱动小鼠（Golshani / Hong）的亲缘关系调查和草原田鼠的不同形式的依恋 （唐纳森）和蝙蝠（亚尔采夫）。为了检验这个假设，我们将完善并使用新一代开源软件 无线微型显微镜（Aharoni），可以长时间记录大量神经元群 在自由行为的动物中。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，我们将对小鼠、草原田鼠和蝙蝠进行体内钙成像以进行测试 交配经历调节 CA2 神经动力学以及 CA2 活动模式编码的假设 空间和身份信息。我们假设，与交配伙伴形成依恋的物种、活动 模式将区分首选合作伙伴与非首选合作伙伴。在目标 2 中，我们将使用化学遗传学抑制 所有物种中的 CA2 以确定 CA2 是否因果驱动亲和和依恋行为。在目标 3 中，我们 将检验以下假设：抑制 CA2 的加压素输入会降低 CA2 的维数 交配后的种群活动模式会减少所有物种、田鼠和蝙蝠对配偶的记忆， 降低前一个交配伙伴身份的可解码性。本着技术发展的目标，我们将 开发并测试具有远距离充电功能的“真正无线”数字数据传输显微镜 能够在无需人工干预的情况下长时间成像数小时。

项目成果

Nucleus accumbens dopamine release reflects the selective nature of pair bonds.

伏隔核多巴胺的释放反映了成对键的选择性性质。

• DOI: 10.1016/j.cub.2023.12.041
• 发表时间: 2024
• 期刊: Current biology : CB
• 作者: Pierce,AnneF;Protter,DavidSW;Watanabe,YurikaL;Chapel,GabrielD;Cameron,RyanT;Donaldson,ZoeR
• 通讯作者: Donaldson,ZoeR

Neural basis of prosocial behavior.

• DOI: 10.1016/j.tins.2022.06.008
• 发表时间: 2022-10
• 期刊: TRENDS IN NEUROSCIENCES
• 影响因子: 15.9
• 作者: Wu, Ye Emily;Hong, Weizhe
• 通讯作者: Hong, Weizhe