小鼠救援样行为及其神经分子机制研究
文献类型：学位论文
| 作者 | 张峰瑞 |
| 答辩日期 | 2023-10 |
| 文献子类 | 博士 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 胡理 |
| 关键词 | 救援样行为 催产素 中央杏仁核 终纹床核 下丘脑室旁核 |
| 学位名称 | 理学博士 |
| 学位专业 | 认知神经科学 |
| 其他题名 | Molecular and neural mechanisms of rescue-like behavior in mice |
| 中文摘要 | In this competitive and conflict-ridden modern society, prosocial behavior contributes to social harmony, survival, reproduction, and cultural transmission in social groups. Among the multifaceted spectrum of prosocial behaviors, acts of rescue and assistance represent an advanced form of prosociality. For instance, human heroism often involves self-sacrifice to aid others. Beyond the human realm, instances of spontaneous rescue-like behaviors have been documented in various species, including primates, whales, and dolphins. Within the controlled confines of laboratory settings, researchers have successfully demonstrated that rats can acquire the ability to rescue trapped peers through training. However, the fundamental question of whether mice can spontaneously engage in rescue-like behaviors devoid of explicit incentives remains a subject of ongoing debate. The present study, through the observation of mouse behavior, reveals that mice engage in behaviors such as grooming, licking, and gentle prodding towards conspecifics in a state of anesthesia. By quantifying and controlling experimental factors, a new binary social behavior paradigmthe mouse rescue-like behavior paradigmis established. This study marks the first evidence that mice can spontaneously perform rescue-like behavior to expedite the recovery of an anesthetized conspecific, and this rescue paradigm occurs naturally among mice without prior training. Upon further investigation of this rescue-like behavior, the study reveals that the essential process involves the demonstrator mouse in distress releasing pheromones that induce stress in the observer mouse. In response to the stress, the observer mouse, in order to reduce their own stress levels, exhibits typical prosocial behaviors towards the stressor (i.e., the demonstrator mouse), such as grooming and licking. Interestingly, throughout the entire rescue process, both the observer and demonstrator mice, solely through their stereotypical behaviors and physiological responses, coordinate with each other to perform what appears to be a "sophisticated" rescue-like behavior, aiding their companions/self in escaping danger. This reflects the preadaptive characteristics and cryptic genetic variation in the process of biological evolution, where certain phenotypes and traits that are not typically expressed can play a crucial role in ensuring the survival of a species under special circumstances. Utilizing this rescue-like behavior paradigm, the present study employed techniques such as transgenic mice, chemogenetics, optogenetics, fiber photometry, and computational neuroscience to further explore the neural mechanisms underlying mouse rescue-like behavior. The experiments reveal that, during rescue-like behavior, oxytocin (OXT) neurons in the paraventricular nucleus of hypothalamus (PVN) release OXT to the central amygdala (CeA) and dorsal bed nucleus of the stria terminalis (dBNST), subsequently activating OXT receptors (OXTR) in CeA and dBNST neurons. Furthermore, the present study finds that the OXT''vN-OXTRCea and OXT''vN-OXTR}NST pathways mediate the emotional and motor functions of rescue-like behavior, respectively. Lastly, through a meticulous analysis and quantification of calcium signals and dynamics of oxytocin within these two neural pathways, the present study delineated strikingly disparate temporal and response patterns of these two pathways. The OXTPVN-OXTRCea pathway exhibits transient responses at the initiation of rescue-like behavior, acting as an emotional trigger facilitating the rescue process. In stark contrast, the OXTPVN-OXTRdBNST pathway manifests a highly synchronized response pattern with licking behavior, governing the motor function of rescue-like behavior. In summary, the present study establishes the groundbreaking experimental paradigm of spontaneous rescue-like behavior in mice, shedding light on the mechanisms through which two parallel OXT signaling pathways, PVN-CeA and PVN-dBNST, mediate rescue-like behavior with varying response patterns, encompassing emotional and motor functions. |
| 英文摘要 | 在当今充满竞争和冲突的现代社会背景下，亲社会行为已经在学术界引起广泛关注。这些亲社会行为有助于促进社会和谐的发展，对社会群体的生存、繁衍以及文化传承起到了积极的作用。在亲社会行为的不同形式中，救援和救助行为代表了一种较为高级的表现，包括人类英雄主义行为，即个人为了拯救他人而牺牲自己。此外，自发的救援行为也在其他物种中有所观察，如灵长类动物、鲸鱼和海豚。在实验室环境中，有研究者通过训练发现了大鼠能够学会如何解救被困的同伴，但小鼠是否能够在没有明确回报的情况下展示自发的救援行为，仍然存在争议。 本研究通过观察小鼠的行为，发现了小鼠能够对处于麻醉状态的同伴展现出一系列行为，包括理毛、舔敌和轻推等，这些行为有助于麻醉的同伴更快地苏醒。通过量化和对各种因素的控制，我们建立了一种新的小鼠二元社交行为范式，即小鼠救援样行为范式。这是首次证明小鼠能够自发地对处于麻醉状态的同伴展示救援行为，以加速同伴的苏醒过程。并且这一救援行为范式不需要特别的训练，而是自然而然地发生在小鼠之间。 随着对这种救援行为的深入研究，本研究发现救援过程的本质是，处于危险状态的示教鼠释放信息素，使周围的观察鼠进入应激状态。这些应激状态的观察鼠为了降低自身的应激水平，展示了一系列典型的亲社会行为，如理毛和舔敌等。这些行为恰好也有助于昏迷的示教鼠迅速苏醒。有趣的是，在整个救援行为过程中，观察鼠和示教鼠仅凭借本能行为和生理反应，就能够相互协作，展示看似高度复杂的救援行为，以帮助同伴或自己摆脱危险。这表明了生物进化中预适应性(preadaptation)和隐性复杂性(cryptic genetic variation)的概念，即一些在平常情况下不显著的特质和性状，在特殊情况下却能够为物种的生存提供关键保障。 基于上述救援行为范式，本研究应用转基因小鼠、化学遗传学、光遗传学、光纤记录以及神经计算等先进技术，进一步深入探讨了小鼠救援行为的神经机制实验结果表明，在救援过程中，观察鼠的下丘脑室旁核(paraventricular nucleus of hypothalamus, PVN)中的催产素(oxytocin, OXT)神经元释放OXT，分别作用于中央杏仁核(central amygdala, CeA)和背侧终纹床核(dorsal bed nucleus of thestriaterminalis, dBNST)，并通过催产素受体(oxytocin receptor, OXTR)激活CeA和dBNST的OXTR神经元。并且发现OXTPVN-OXTRCeA和OXTPVN-OXTRdBNST这两条神经通路分别控制了救援样行为的情绪启动功能和运动执行功能。 此外，通过分析和量化这两条神经通路内钙信号和催产素的动态变化，本研究发现在救援样行为中，这两条神经通路的时空动态和响应模式表现出截然不同的特征。OXTPVN-OXTRCeA通路主要在救援样行为开始的时候出现瞬时响应，作为情绪的诱发器来促进救援样行为;而OXTPVN-OXTRdBNST通路表现出与救援样行为高度同步的响应模式，控制了救援样行为的运动功能。 综上，本研究建立提出了小鼠自发救援样行为的实验范式，并揭示了PVN-CeA和PVN-dBNST两条平行的OXT信号通路以不同的响应模式分别介导了救援样行为的情绪功能和运动功能。为亲社会行为神经机制的研究，提出了关键的证据和理论模型。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/46616]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 张峰瑞. 小鼠救援样行为及其神经分子机制研究[D]. 中国科学院心理研究所. 中国科学院大学. 2023. |
入库方式： OAI收割
来源：心理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。