Calvin Olivia L, Erickson Matthew T, Walters Cody J, Redish A David
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS Biol. 2025 Jan 14;23(1):e3002954. doi: 10.1371/journal.pbio.3002954. eCollection 2025 Jan.
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 cycles. Similarly, important information that is distant from the animal's position is represented during hippocampal high-synchrony events (HSEs), which coincide 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 decoding of the pseudo-predator's location 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 (LFPs), 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特征。当个体面临趋近-回避冲突时，对未来事件的这种担忧尤为重要。已知在θ节律期间，趋近的潜在目标在背侧海马体中得到表征。同样，与动物位置有一定距离的重要信息在海马体高同步事件（HSEs）期间得到表征，而海马体高同步事件与尖波涟漪（SWRs）同时出现。未来潜在威胁可能也会以类似方式得到表征。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-回避冲突过程中海马体内威胁和奖励是如何被表征的。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节律期间，能够解码类捕食者的位置。在第一次攻击之后，我们观察到新的位置野出现在机器人所在位置（而非大鼠被攻击时的位置）。抗焦虑药物地西泮减少了类似焦虑的行为，并改变了海马体局部场电位（LFPs），包括减少了尖波涟漪，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作用靶点。
