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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763333
• 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生物做出决定并执行与环境相适应的行为。在某些情况下，需要在很少或没有事先了解情况的情况下立即做出决定。例如，当面对未知的威胁时，动物必须识别威胁，计算威胁等级，然后从一系列行为中做出选择。这些可能是天生的（未学习的）或学习的行为。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，动物会优先考虑一个而不是另一个吗？目前的观点是，先天行为比后天的生存策略更重要。然而，我们的初步工作表明，这种等级制度是可以被打破的。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，这些神经网络在学习行为和先天行为中都至关重要。我们将使用小鼠作为模型来研究先天防御/生存行为；我们的范例模拟了从天而降的威胁（飞行的掠食者）。这个若隐若现和下降的阴影模拟了来自接近的捕食者的威胁迫切性的增加；它需要视觉信息处理，并驱动防御行为——要么逃到避难所，要么冻死。在没有捕食者任务经验的实验室小鼠中，这种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神经元在对阴影的反应中增加了它们的活动，并似乎预测了逃跑的行为决定。我们会问，CRH神经元活动特征的这种增加是否是预备事件序列的预期组成部分，这些事件序列允许动物进行计算，最终导致逃跑行为。我们也有令人信服的证据表明，CRH神经元预测逃跑的活动可以通过与迫在眉睫的捕食者无关的工具学习范式进行修改，但依赖于厌恶刺激之前的中性线索。这表明这些细胞可能是连接先天行为和习得行为的交叉点。我们的实验室和其他实验室最近的研究表明，CRH神经元可能是皮层下或自下而上回路的一部分，它将生物体的状态信息传递给更高的大脑区域。在这里，我们建议使用先天和习得的行为范式，结合体内纤维光度法、光遗传学、一种新开发的用于评估自发行为的机器学习算法和体外电生理学来验证工具可控制性训练改变CRH神经元活动以改变先天行为优先级的假设。