The neural mechanisms by which stress prevents empathy in mice

压力阻止小鼠同理心的神经机制

• 批准号: RGPIN-2016-06284
• 负责人: Martin, Loren
• 金额: $ 2.4万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709883
• 关键词: neural; mechanisms; stress; prevents; empathy

Empathy has deep evolutionary roots. It is a fundamental process required for social behaviour and allows the understanding of emotions by sharing sensory and affective states with other individuals. Even the most advanced forms of empathy in humans are built on more basic forms and remain connected to core mechanisms. Empathic responses comprise cognitive, affective, and emotional components, and are modulated by situational and contextual factors. From a neuroscientific perspective this suggests that distinct neural mechanisms underlie different types of empathy-related responses. Given the complexity of empathy, investigation of its neurobiological underpinnings would be meaningless without breaking it down into component processes. An increasing amount of evidence suggests that the core components of empathy are shared among rodents and non-human mammals and neurohormones such as oxytocin and cortisol regulate these behaviours. In fact, a number of studies have indicated that oxytocin and cortisol regulate each other to influence social behaviours, but the mechanism underlying this remains unknown. The current proposal will focus on the reciprocal modulation of the stress-related neuropeptide corticotrophinreleasing hormone (CRH) and oxytocin in regulating rodent empathy. To accomplish this, we will examine the stress response as a modifier of rodent empathy by using a combination of behaviour, chemoogenetics, electrophysiology, biochemical and immunohistochemical assessment. Specifically, we will use chemogenetics to selectively dissect specific populations of neurons and determine whether CRH and/or oxytocin neurons directly regulate each other to modify empathy and affective behaviours. In addition, we will identify the synaptic and receptor changes that occur in stress-related brain regions that prevent empathy; we will then reverse these changes with in vivo pharmacology. Thus, our research program will examine the neural mechanism by which stress-related brain circuitry regulates affective communication in rodents to modulate sensory output this is rarely if ever done from a basic science perspective. Second, although many experiments will measure pain behaviour or response to pain behaviour of another, we are simply using pain to evoke social and affective communication. Thus, the proposed studies will provide insight into the fundamental mechanisms that engage the neural circuits responsible for empathylike behaviours and will shed light into the molecular mechanisms that are necessary for these behaviours.

移情有着深刻的进化根源。它是社会行为所需的一个基本过程，并允许通过与其他人分享感官和情感状态来理解情感。即使是人类最先进的共情形式，也是建立在更基本的形式之上，并与核心机制保持联系。移情反应包括认知、情感和情绪成分，并受情境和背景因素的调节。从神经科学的角度来看，这表明不同的神经机制是不同类型的共情相关反应的基础。鉴于共情的复杂性，如果不将其分解为各个组成过程，那么对其神经生物学基础的研究就毫无意义。越来越多的证据表明，同情心的核心成分在啮齿动物和非人类哺乳动物中是共享的，催产素和皮质醇等神经激素调节这些行为。事实上，许多研究表明，催产素和皮质醇相互调节，影响社会行为，但其背后的机制仍然未知。目前的建议将集中在相互调制的压力相关的神经肽促肾上腺皮质激素释放激素（CRH）和催产素调节啮齿动物的同情。要做到这一点，我们将研究的压力反应作为啮齿动物的移情的修饰符，通过使用行为，化学遗传学，电生理学，生物化学和免疫组织化学评估的组合。具体来说，我们将使用化学遗传学来选择性地解剖特定的神经元群体，并确定CRH和/或催产素神经元是否直接相互调节，以改变共情和情感行为。此外，我们将确定在与压力相关的大脑区域中发生的突触和受体变化，这些变化会阻止共情;然后我们将用体内药理学逆转这些变化。因此，我们的研究计划将研究神经机制，通过这种机制，与压力相关的大脑回路调节啮齿动物的情感交流，以调节感觉输出，这从基础科学的角度来看是很少的。第二，虽然许多实验会测量疼痛行为或对他人疼痛行为的反应，但我们只是利用疼痛来唤起社会和情感交流。 因此，拟议的研究将深入了解负责同情样行为的神经回路的基本机制，并将阐明这些行为所必需的分子机制。