Baker Phillip M, Mathis Victor, Lecourtier Lucas, Simmons Sarah C, Nugent Fereshteh S, Hill Sierra, Mizumori Sheri J Y
Department of Psychology, Seattle Pacific University, Seattle, WA, United States.
CNRS UPR 3212, Institut des Neurosciences Cellulaires et Intégratives, Center National de la Recherche Scientifique, University of Strasbourg, Strasbourg, France.
Front Syst Neurosci. 2022 Mar 3;16:826475. doi: 10.3389/fnsys.2022.826475. eCollection 2022.
In this Perspective review, we highlight some of the less explored aspects of lateral habenula (LHb) function in contextual memory, sleep, and behavioral flexibility. We provide evidence that LHb is well-situated to integrate different internal state and multimodal sensory information from memory-, stress-, motivational-, and reward-related circuits essential for both survival and decision making. We further discuss the impact of early life stress (ELS) on LHb function as an example of stress-induced hyperactivity and dysregulation of neuromodulatory systems within the LHb that promote anhedonia and motivational deficits following ELS. We acknowledge that recent technological advancements in manipulation and recording of neural circuits in simplified and well-controlled behavioral paradigms have been invaluable in our understanding of the critical role of LHb in motivation and emotional regulation as well as the involvement of LHb dysfunction in stress-induced psychopathology. However, we also argue that the use of ethologically-relevant behaviors with consideration of complex aspects of decision-making is warranted for future studies of LHb contributions in a wide range of psychiatric illnesses. We conclude this Perspective with some of the outstanding issues for the field to consider where a multi-systems approach is needed to investigate the complex nature of LHb circuitry interactions with environmental stimuli that predisposes psychiatric disorders.
在这篇观点性综述中，我们重点介绍了外侧缰核（LHb）在情境记忆、睡眠和行为灵活性方面一些尚未充分探索的功能。我们提供的证据表明，LHb处于良好位置，可整合来自记忆、应激、动机和奖励相关回路的不同内部状态和多模态感觉信息，这些信息对于生存和决策至关重要。我们进一步讨论了早期生活应激（ELS）对LHb功能的影响，作为应激诱导的LHb内神经调节系统多动和失调的一个例子，这种失调会在ELS后促进快感缺失和动机缺陷。我们认识到，近期在简化且严格控制的行为范式中对神经回路进行操纵和记录的技术进步，对于我们理解LHb在动机和情绪调节中的关键作用以及LHb功能障碍在应激诱导的精神病理学中的作用具有不可估量的价值。然而，我们也认为，在未来研究LHb在广泛精神疾病中的作用时，考虑决策的复杂方面并使用与行为学相关的行为是必要的。我们在这篇观点性综述结尾提出了该领域需要考虑的一些突出问题，其中需要采用多系统方法来研究LHb神经回路与易引发精神疾病的环境刺激相互作用的复杂性质。
