Table_1_Interoceptive Insular Cortex Mediates Both Innate Fear and Contextual Threat Conditioning to Predator Odor.XLSX

The insular cortex (IC), among other brain regions, becomes active when humans experience fear or anxiety. However, few experimental studies in rats have implicated the IC in threat responses. We have recently reported that inactivation of the primary interoceptive cortex (pIC) during pre-training, or the intra-pIC blockade of protein synthesis immediately after training, impaired the consolidation of auditory fear conditioning. The present study was designed to investigate the role of the pIC in innate and learned defensive responses to predator odor. Freezing behavior was elicited by single or repetitive exposures to a collar that had been worn by a domestic cat. Sessions were video-recorded and later scored by video observation. We found that muscimol inactivation of the pIC reduced the expression of freezing reaction in response to a single or repeated exposure to cat odor. We also found that pIC inactivation with muscimol impaired conditioning of fear to the context in which rats were exposed to cat odor. Furthermore, neosaxitoxin inactivation of the pIC resulted in a prolonged and robust reduction in freezing response in subsequent re-exposures to cat odor. In addition, freezing behavior significantly correlated with the neural activity of the IC. The present results suggest that the IC is involved in the expression of both innate and learned fear responses to predator odor.

当人类经历恐惧或焦虑情绪时，岛叶皮层（insular cortex，IC）与其他多个脑区一样会被激活。然而，针对大鼠的相关实验研究中，极少有研究证实岛叶皮层参与威胁应对反应。我们此前曾报道，在训练前对初级内感受皮层（primary interoceptive cortex，pIC）进行灭活，或是在训练结束后立即通过pIC脑区局部给药阻断蛋白质合成，均会损害听觉恐惧条件反射的记忆巩固。本研究旨在探究初级内感受皮层在大鼠面对捕食者气味时介导的先天与后天防御反应中的作用。通过让大鼠单次或重复接触家猫佩戴过的项圈，诱发其僵立行为。实验过程全程录像，后续通过视频观察对行为进行评分。我们发现，通过蝇蕈醇对初级内感受皮层进行灭活，能够降低大鼠在单次或重复接触猫气味时的僵立行为表现。此外，我们还发现，通过蝇蕈醇灭活初级内感受皮层，会损害大鼠在接触猫气味的情境中形成的恐惧条件反射。进一步实验显示，通过新蛤蚌毒素灭活初级内感受皮层，会在后续再次接触猫气味时，使僵立反应出现长时间且显著的减弱。此外，僵立行为与岛叶皮层的神经活动呈现显著相关性。本研究结果表明，岛叶皮层参与了大鼠面对捕食者气味时的先天与后天恐惧反应的表达过程。