Cheung Kathy Y M, Nair Aditya, Li Ling-Yun, Shapiro Mikhail G, Anderson David J
bioRxiv. 2024 Aug 13:2024.08.12.607651. doi: 10.1101/2024.08.12.607651.
Hypothalamic VMHdm neurons are activated by predator cues and are necessary and sufficient for instinctive defensive responses. However, such data do not distinguish which features of a predator encounter are encoded by VMHdm neural activity. To address this issue, we imaged VMHdm neurons at single-cell resolution in freely behaving mice exposed to a natural predator in varying contexts. Our results reveal that VMHdm neurons do not represent different defensive behaviors, but rather encode predator identity and multiple predator-evoked internal states, including threat-evoked fear/anxiety; neophobia or arousal; predator imminence; and safety. Notably, threat and safety are encoded bi-directionally by anti-correlated subpopulations. Finally, individual differences in predator defensiveness are correlated with differences in VMHdm response dynamics. Thus, different threat-related internal state variables are encoded by distinct neuronal subpopulations within a genetically defined, anatomically restricted hypothalamic cell class.
Distinct subsets of VMHdm neurons encode multiple predator-evoked internal states. Anti-correlated subsets encode safety vs. threat in a bi-directional mannerA population code for predator imminence is identified using a novel assay VMHdm dynamics correlate with individual variation in predator defensiveness.
下丘脑腹内侧核背内侧部(VMHdm)神经元可被捕食者线索激活,对本能防御反应而言是必要且充分的。然而,此类数据并未区分捕食者遭遇的哪些特征是由VMHdm神经活动编码的。为解决这一问题,我们在自由活动的小鼠处于不同情境下接触自然捕食者时,以单细胞分辨率对VMHdm神经元进行成像。我们的结果表明,VMHdm神经元并不代表不同的防御行为,而是编码捕食者身份和多种捕食者诱发的内部状态,包括威胁诱发的恐惧/焦虑;新事物恐惧症或觉醒;捕食者逼近;以及安全状态。值得注意的是,威胁和安全状态由反相关的亚群进行双向编码。最后,捕食者防御方面的个体差异与VMHdm反应动态的差异相关。因此,不同的威胁相关内部状态变量由基因定义、解剖学上受限的下丘脑细胞类群中的不同神经元亚群进行编码。
VMHdm神经元的不同亚群编码多种捕食者诱发的内部状态。反相关亚群以双向方式编码安全与威胁。使用一种新方法确定了捕食者逼近的群体编码。VMHdm动态与捕食者防御中的个体差异相关。