Hones Victoria I, Mizumori Sheri J Y
Department of Psychology, University of Washington, Seattle, WA, United States.
Graduate Program in Neuroscience, University of Washington, Seattle, WA, United States.
Front Behav Neurosci. 2022 Apr 4;16:852235. doi: 10.3389/fnbeh.2022.852235. eCollection 2022.
The ability to make appropriate decisions that result in an optimal outcome is critical for survival. This process involves assessing the environment as well as integrating prior knowledge about the environment with information about one's current internal state. There are many neural structures that play critical roles in mediating these processes, but it is not yet known how such information coalesces to influence behavioral output. The lateral habenula (LHb) has often been cited as a structure critical for adaptive and flexible responding when environmental contexts and internal state changes. A challenge, however, has been understanding how LHb promotes response flexibility. In this review, we hypothesize that the LHb enables flexible responding following the integration of context memory and internal state information by signaling downstream brainstem structures known to drive hippocampal theta. In this way, animals respond more flexibly in a task situation not because the LHb selects a particular action, but rather because LHb enhances a hippocampal neural state that is often associated with greater attention, arousal, and exploration. In freely navigating animals, these are essential conditions that are needed to discover and implement appropriate alternative choices and behaviors. As a corollary to our hypothesis, we describe short- and intermediate-term functions of the LHb. Finally, we discuss the effects on the behavior of LHb dysfunction in short- and intermediate-timescales, and then suggest that new therapies may act on the LHb to alleviate the behavioral impairments following long-term LHb disruption.
做出能产生最优结果的恰当决策的能力对生存至关重要。这个过程涉及评估环境，以及将关于环境的先验知识与关于自身当前内部状态的信息整合起来。有许多神经结构在介导这些过程中发挥着关键作用，但目前尚不清楚这些信息是如何聚合以影响行为输出的。外侧缰核（LHb）常被认为是在环境背景和内部状态变化时对适应性和灵活反应至关重要的结构。然而，一个挑战在于理解LHb如何促进反应灵活性。在这篇综述中，我们假设LHb通过向已知驱动海马体θ波的下游脑干结构发出信号，在整合情境记忆和内部状态信息后实现灵活反应。通过这种方式，动物在任务情境中反应更灵活，并非因为LHb选择了特定行动，而是因为LHb增强了一种通常与更高注意力、唤醒和探索相关的海马体神经状态。在自由活动的动物中，这些是发现和实施适当替代选择及行为所需的基本条件。作为我们假设的一个推论，我们描述了LHb的短期和中期功能。最后，我们讨论了短期和中期时间尺度上LHb功能障碍对行为的影响，然后提出新的疗法可能作用于LHb以减轻长期LHb破坏后的行为损伤。
