Calvin Olivia L, Erickson Matthew T, Walters Cody J, Redish A David
Department of Neuroscience, University of Minnesota, Minneapolis MN 55455.
bioRxiv. 2024 Mar 12:2024.03.10.584295. doi: 10.1101/2024.03.10.584295.
Worrying about perceived threats is a hallmark of multiple psychological disorders including anxiety. This concern about future events is particularly important when an individual is faced with an approach-avoidance conflict. Potential goals to approach are known to be represented in the dorsal hippocampus during theta sweeps. Similarly, important non-local information is represented during hippocampal high synchrony events (HSEs), which are correlated with sharp-wave ripples (SWRs). It is likely that potential future threats may be similarly represented. We examined how threats and rewards were represented within the hippocampus during approach-avoidance conflicts in rats faced with a predator-like robot guarding a food reward. We found representations of the pseudo-predator during HSEs when hesitating in the nest, and during theta prior to retreating as the rats approached the pseudo-predator. After the first attack, we observed new place fields appearing at the location of the robot (not the location the rat was when attacked). The anxiolytic diazepam reduced anxiety-like behavior and altered hippocampal local field potentials, including reducing SWRs, suggesting that one potential mechanism of diazepam's actions may be through altered representations of imagined threat. These results suggest that hippocampal representation of potential threats could be an important mechanism that underlies worry and a potential target for anxiolytics.
担忧感知到的威胁是包括焦虑症在内的多种心理障碍的一个标志。当个体面临趋近-回避冲突时,这种对未来事件的担忧尤为重要。已知在θ波扫描期间,趋近的潜在目标在背侧海马体中得到表征。同样,重要的非局部信息在海马体高同步事件(HSEs)期间得到表征,这些事件与尖波涟漪(SWRs)相关。未来潜在的威胁可能也会以类似的方式得到表征。我们研究了在面对守护食物奖励的类捕食者机器人时,大鼠在趋近-回避冲突期间威胁和奖励在海马体中是如何被表征的。我们发现,当大鼠在巢穴中犹豫时,以及在接近类捕食者机器人并撤退之前的θ波期间,类捕食者的表征出现在HSEs期间。第一次攻击后,我们观察到新的位置野出现在机器人所在位置(而非大鼠被攻击时所在位置)。抗焦虑药物地西泮减少了焦虑样行为,并改变了海马体局部场电位,包括减少SWRs,这表明地西泮作用的一种潜在机制可能是通过改变对想象威胁的表征。这些结果表明,海马体对潜在威胁的表征可能是担忧背后的一个重要机制,也是抗焦虑药物的一个潜在靶点。