Hypothalamic CRH neurons and the control of innate behaviour

下丘脑 CRH 神经元和先天行为的控制

• 批准号: RGPIN-2019-07175
• 负责人: Bains, Jaideep
• 金额: $ 3.42万
• 依托单位: University of Calgary
• 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=716400
• 关键词: Hypothalamic; CRH; neurons; control; innate

Navigating the world requires that all organisms make decisions and execute behaviors that are context appropriate. In some situations, an instantaneous decision with little or no prior knowledge of the situation, is required. For example, when faced with an unknown threat, the animal must recognize the threat, compute threat level and then choose from a palette of behaviors. These may be innate (unlearned) or learned behaviors. The correct choice is necessary to ensure survival. How do innate and learned behaviors intersect? Are there specific conditions under which animals prioritize one above another? The current view is that innate behaviors are prioritized over learned survival tactics. Yet, our preliminary work suggests that this hierarchy can be disrupted. Here we will ask whether specific behavioral training can shift these innate strategies by modifying the output of neural networks that are critically involved in both learned and innate behavior. We will use mice as a model to investigate innate defensive/survival behaviors; our paradigm mimics threat descending from above (flying predators). This looming and descending shadow mimics an increase in threat imminence from an approaching predator; it requires visual information processing and drives defensive behavior either an escape targeted to a shelter, or freezing. In lab mice, with no prior experience with a predator task, the response is the consequence of accessing an unlearned behavioral repertoire. Our preliminary data indicate that CRH neurons in the paraventricular nucleus of the hypothalamus increase their activity in response to a looming shadow and appear to anticipate the behavioral decision to escape. We will ask whether that this ramping in the neuronal activity signature of CRH neurons is an anticipatory component of a preparatory sequence of events that allows the animal to make a calculation that culminates in escape behavior. We also have compelling evidence that the activity of CRH neurons to anticipate escape can be modified through instrumental learning paradigms that are unrelated to the looming predator, but rely on a neutral cue prior to an aversive stimulus. This indicates that these cells may be an intersectional node that links innate and learned behavior. Recent work from our lab, and other, shows that CRH neurons may be part of a subcortical, or bottom-up circuit that relays information about the state of the organism to higher brain regions. Here we propose to use innate and learned behavioral paradigms, combined with in vivo fibre photometry, optogenetics, a newly developed machine learning algorithm for assessing spontaneous behaviors and in vitro electrophysiology to test the hypothesis that instrumental controllability training alters CRH neuron activity to shift innate behavioral priorities.

在世界上航行需要所有的有机体做出决策并执行与环境相适应的行为。在某些情况下，需要在事先对情况了解很少或不了解的情况下立即作出决定。例如，当面对未知的威胁时，动物必须识别威胁，计算威胁级别，然后从行为选项板中进行选择。这些行为可能是先天的（非习得的）或习得的。正确的选择是确保生存的必要条件。先天行为和习得行为是如何交叉的？在特定的条件下，动物会优先考虑其中一个吗？目前的观点是，先天行为优先于学习的生存策略。然而，我们的初步工作表明，这种层次结构可以被打乱。在这里，我们将询问特定的行为训练是否可以通过修改神经网络的输出来改变这些先天策略，这些神经网络在习得行为和先天行为中都有重要作用。 我们将使用小鼠作为研究先天防御/生存行为的模型;我们的范例模仿来自上方的威胁（飞行捕食者）。这种若隐若现和下降的阴影模拟了来自接近的捕食者的威胁紧迫性的增加;它需要视觉信息处理，并驱动防御行为，要么是逃跑到避难所，要么是冻结。在实验室小鼠中，没有捕食者任务的经验，反应是访问未学习的行为库的结果。我们的初步数据表明，下丘脑室旁核的CRH神经元增加其活动，以应对一个迫在眉睫的阴影，并出现预期的行为决定逃跑。我们要问的是，CRH神经元的神经元活动特征的这种斜坡是否是一系列事件的预备性组成部分，这些事件允许动物进行计算，最终导致逃跑行为。我们也有令人信服的证据表明，CRH神经元的活动，以预期逃脱可以通过工具学习范式，是无关的迫在眉睫的捕食者，但依赖于一个中性的线索之前，厌恶的刺激修改。这表明这些细胞可能是连接先天行为和习得行为的交叉节点。 我们实验室和其他实验室最近的工作表明，CRH神经元可能是皮层下或自下而上电路的一部分，该电路将有关生物体状态的信息传递到更高的大脑区域。在这里，我们建议使用先天和学习的行为范例，结合体内纤维光度学，光遗传学，一种新开发的机器学习算法，用于评估自发行为和体外电生理学，以测试工具可控性训练改变CRH神经元活动以改变先天行为优先级的假设。