Instituto de Fisiología y Biofísica "Bernardo Houssay" (IFIBIO-Houssay), Grupo de Neurociencia de Sistemas, Universidad de Buenos Aires y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
CERVO Brain Research Center, Department of Psychiatry and Neurosciences, Université Laval, Quebec City, Quebec, Canada.
Neuropsychopharmacology. 2022 May;47(6):1210-1219. doi: 10.1038/s41386-022-01294-5. Epub 2022 Feb 25.
Fear is an extreme form of aversion that underlies pathological conditions such as panic or phobias. Fear conditioning (FC) is the best-understood model of fear learning. In FC the context and a cue are independently associated with a threatening unconditioned stimulus (US). The lateral habenula (LHb) is a general encoder of aversion. However, its role in fear learning remains poorly understood. Here we studied in rats the role of the LHb in FC using optogenetics and pharmacological tools. We found that inhibition or activation of the LHb during entire FC training impaired both cued and contextual FC. In contrast, optogenetic inhibition of the LHb restricted to cue and US presentation impaired cued but not contextual FC. In either case, simultaneous activation of contextual and cued components of FC, by the presentation of the cue in the training context, recovered the conditioned fear response. Our results support the notion that the LHb is required for the formation of independent contextual and cued fear memories, a previously uncharacterized function for this structure, that could be critical in fear generalization.
恐惧是一种极端的厌恶形式，是恐慌或恐惧症等病理状况的基础。恐惧条件反射 (FC) 是恐惧学习中研究得最透彻的模型。在 FC 中，上下文和提示与威胁性非条件刺激 (US) 独立相关联。外侧缰核 (LHb) 是厌恶的一般编码器。然而，其在恐惧学习中的作用仍知之甚少。在这里，我们使用光遗传学和药理学工具在大鼠中研究了 LHb 在 FC 中的作用。我们发现，在整个 FC 训练过程中抑制或激活 LHb 会损害提示和上下文 FC。相比之下，仅在提示和 US 呈现期间抑制 LHb 的光遗传学抑制会损害提示性但不损害上下文 FC。在这两种情况下，通过在训练环境中呈现提示，同时激活 FC 的上下文和提示成分，恢复了条件性恐惧反应。我们的结果支持了这样一种观点，即 LHb 是形成独立的上下文和提示性恐惧记忆所必需的，这是该结构以前未被描述的功能，它可能对恐惧泛化至关重要。
