The neural mechanisms by which stress prevents empathy in mice

同理心有着深刻的进化根源。它是社会行为所需的基本过程，并允许通过与其他个体分享感觉和情感状态来理解情绪。即使是人类最先进的移情形式，也是建立在更基本的形式之上，并与核心机制保持联系。共情反应包括认知、情感和情绪成分，并受情境和语境因素的调节。从神经科学的角度来看，这表明不同的神经机制构成了不同类型的共情相关反应的基础。考虑到移情的复杂性，如果不将其分解成各个组成过程，对其神经生物学基础的研究将毫无意义。越来越多的证据表明，在啮齿类动物和非人类哺乳动物中，移情的核心成分是相同的，催产素和皮质醇等神经激素调节着这些行为。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，但其背后的机制尚不清楚。目前的建议将重点放在应激相关神经肽促肾上腺皮质激素释放激素（CRH）和催产素在调节啮齿动物共情中的相互调节。为了实现这一目标，我们将通过结合行为、化学遗传学、电生理学、生化和免疫组织化学评估来研究应激反应作为啮齿动物共情的修饰因子。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，以改变移情和情感行为。此外，我们将确定发生在压力相关大脑区域的突触和受体变化，这些变化会阻止移情；然后我们将用体内药理学逆转这些变化。因此，我们的研究计划将检查啮齿动物的神经机制，通过压力相关的大脑回路调节情感交流来调节感觉输出，这是很少从基础科学的角度进行的。第二，尽管许多实验将测量疼痛行为或对他人疼痛行为的反应，但我们只是用疼痛来唤起社会和情感交流。因此，所提出的研究将提供对参与负责共情行为的神经回路的基本机制的见解，并将阐明这些行为所必需的分子机制。**

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. **