Department of Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, 72076 Tübingen, Germany.
Department of Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, 72076 Tübingen, Germany
eNeuro. 2024 Aug 19;11(8). doi: 10.1523/ENEURO.0063-24.2024. Print 2024 Aug.
Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. The reciprocal connectivity between the locus ceruleus (LC) and ACC is thought to support behavioral reorganization triggered by the detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats and trained rats on a spatial task. Subsequently, we altered LC activity and confronted rats with an unexpected change of reward locations. In a new spatial context, rats with decreased noradrenaline (NA) in the ACC entered unbaited maze arms more persistently which was indicative of perseveration. In contrast, the suppression of the global NA transmission reduced perseveration. Neither chemogenetic manipulation nor inactivation of the ACC by muscimol affected the rate of learning, possibly due to partial virus transduction of the LC neurons and/or the compensatory engagement of other prefrontal regions. Importantly, we observed behavioral deficits in rats with LC damage caused by virus injection. The latter finding highlights the importance of careful histological assessment of virus-transduced brain tissue as inadvertent damage of the targeted cell population due to virus neurotoxicity or other factors might cause unwanted side effects. Although the specific role of ACC in the flexibility of spatial behavior has not been convincingly demonstrated, our results support the beneficial role of noradrenergic transmission for an optimal function of the ACC. Overall, our findings suggest the LC exerts the projection-specific modulation of neural circuits mediating the flexibility of spatial behavior.
适应性行为依赖于有效的认知控制。前扣带皮层（ACC）是执行前额叶网络中的一个关键节点。蓝斑（LC）和 ACC 之间的相互连接被认为支持由检测到意外变化触发的行为重组。我们在成年雄性大鼠中用兴奋性或抑制性化学遗传受体转导 LC 神经元，并对大鼠进行空间任务训练。随后，我们改变 LC 的活动并让大鼠面对奖励位置的意外变化。在新的空间环境中，ACC 中去甲肾上腺素（NA）减少的大鼠更持久地进入未诱饵的迷宫臂，这表明存在固执。相比之下，抑制全局 NA 传递减少了固执。化学遗传操作或 muscimol 对 ACC 的失活均未影响学习速度，这可能是由于 LC 神经元的病毒转导不完全和/或其他前额叶区域的代偿性参与。重要的是，我们观察到由于病毒注射导致 LC 损伤的大鼠出现行为缺陷。后一种发现强调了仔细评估病毒转导脑组织的重要性，因为由于病毒神经毒性或其他因素导致目标细胞群体的意外损伤可能会导致不必要的副作用。尽管 ACC 在空间行为灵活性中的具体作用尚未得到令人信服的证明，但我们的结果支持去甲肾上腺素传递对 ACC 最佳功能的有益作用。总的来说，我们的研究结果表明 LC 对介导空间行为灵活性的神经回路施加了特定的投射调制。
