Cell Physiology Institute-Neuroscience, National Autonomous University of Mexico, Mexico City 04510, Mexico.
Cell Physiology Institute-Neuroscience, National Autonomous University of Mexico, Mexico City 04510, Mexico
eNeuro. 2021 Apr 19;8(2). doi: 10.1523/ENEURO.0482-20.2021. Print 2021 Mar-Apr.
Survival depends on the ability to adaptively react or execute actions based on previous aversive salient experiences. Although lateral habenula (LHb) activity has been broadly implicated in the regulation of aversively motivated responses, it is not clear under which conditions this brain structure is necessary to regulate defensive responses to a threat. To address this issue, we combined pharmacological inactivations with behavioral tasks that involve aversive and appetitive events and evaluated defensive responses in rats. We found that LHb pharmacological inactivation did not affect cued threat conditioning (fear) and extinction (safety) learning and memory, anxiety-like or reward-seeking behaviors. Surprisingly, we found that LHb inactivation abolished reactive defensive responses (tone-elicited freezing) only when threat (conditioning) and safety memories (extinction and latent inhibition) compete during retrieval. Consistently, we found that LHb inactivation impaired active defensive responses [platform-mediated avoidance (PMA)], thereby biasing choice behavior (between avoiding a threat or approaching food) toward reward-seeking responses. Together, our findings suggest that LHb activity mediates defensive responses only when guided by competing threat and safety memories, consequently revealing a previously uncharacterized role for LHb in experience-dependent emotional conflict.
生存取决于根据先前厌恶的显著经验适应性地反应或执行动作的能力。尽管外侧缰核（LHb）的活动已被广泛认为与调节厌恶驱动的反应有关，但尚不清楚在何种条件下该脑结构对于调节对威胁的防御反应是必要的。为了解决这个问题，我们结合了药理学失活和涉及厌恶和奖赏事件的行为任务，并评估了大鼠的防御反应。我们发现，LHb 药理学失活不影响提示威胁条件反射（恐惧）和消退（安全）学习和记忆、焦虑样或寻求奖赏的行为。令人惊讶的是，我们发现，只有在检索过程中威胁（条件反射）和安全记忆（消退和潜伏抑制）竞争时，LHb 失活才会消除反应性防御反应（音调和冻结）。一致地，我们发现，LHb 失活损害了主动防御反应[平台介导的回避（PMA）]，从而使回避威胁或接近食物的选择行为偏向于寻求奖赏的反应。总之，我们的发现表明，只有在受到竞争的威胁和安全记忆的指导时，LHb 活性才会介导防御反应，从而揭示了 LHb 在经验依赖的情绪冲突中的一个以前未被描述的作用。
