Hypothalamic CRH neurons and the control of innate behaviour

在世界上航行需要所有的有机体做出决定并执行与环境相适应的行为。在某些情况下，需要在几乎或根本不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，计算威胁级别，然后从一系列行为中进行选择。这些行为可能是与生俱来的，也可能是后天习得的。正确的选择是确保生存所必需的。先天行为和后天行为是如何相交的？有没有特定的条件让动物优先于其他动物？目前的观点是，与生俱来的行为优先于后天的生存策略。然而，我们的初步工作表明，这种等级制度可能会被打破。在这里，我们将询问特定的行为训练是否可以通过改变神经网络的输出来改变这些天生的策略，这些神经网络既涉及学习行为又涉及天生行为。 我们将使用老鼠作为模型来研究天生的防御/生存行为；我们的范例模仿威胁从上方下降(飞行的捕食者)。这种隐约可见的阴影模拟了来自逼近的捕食者的威胁迫在眉睫的增加；它需要视觉信息处理，并驱动防御行为，要么是针对避难所的逃跑，要么是冰冻。在没有捕食者任务经验的实验室小鼠中，这种反应是接触到未学习的行为指令的结果。我们的初步数据表明，下丘脑室旁核中的CRH神经元增加了它们对隐约可见的阴影的反应，似乎预见到了逃避的行为决定。我们会问，CRH神经元神经元活动特征的这种倾斜是否是一系列准备事件的预期组成部分，从而允许动物进行最终导致逃避行为的计算。我们也有令人信服的证据表明，CRH神经元预测逃逸的活动可以通过工具性学习范式来改变，这些范式与迫在眉睫的捕食者无关，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后天行为的交叉节点。 我们实验室和其他实验室最近的研究表明，CRH神经元可能是皮质下或自下而上回路的一部分，该回路将关于有机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后天的行为范式，结合体内纤维光度学、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检验工具可控性训练改变CRH神经元活动从而改变固有行为优先级的假设。

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.