Kim Jae Gon, Ea Ji Yun, Yoon Bong-June
Department of Life Sciences, Korea University, Seoul, Republic of Korea.
Front Mol Neurosci. 2023 Mar 16;16:1140672. doi: 10.3389/fnmol.2023.1140672. eCollection 2023.
Stress is a critical precipitating factor for major depression. However, individual responses to the same stressor vary widely, possibly owing to individual variations in stress resilience. Nevertheless, the factors that determine stress susceptibility and resilience remain poorly understood. Orexin neurons have been implicated in the control of stress-induced arousal. Therefore, we investigated whether orexin-expressing neurons are involved in the regulation of stress resilience in male mice. We found that the level of c-fos expression was significantly different in susceptible versus resilient mice in the learned helplessness test (LHT). Furthermore, activating orexinergic neurons induced resilience in the susceptible group, and this resilience was also consistently observed in other behavioral tests. However, activating orexinergic neurons during the induction period (during inescapable stress exposure) did not affect stress resilience in the escape test. In addition, analyses using pathway-specific optic stimulation revealed that activating orexinergic projections to the medial part of the nucleus accumbens (NAc) alone mediated a decrease in anxiety but was not sufficient to induce resilience in the LHT. Collectively, our data suggest that orexinergic projections to multiple targets control diverse and flexible stress-related behaviors in response to various stressors.
应激是重度抑郁症的一个关键促发因素。然而，个体对同一应激源的反应差异很大，这可能归因于应激恢复力的个体差异。尽管如此，决定应激易感性和恢复力的因素仍知之甚少。食欲素神经元已被证实参与应激诱导的觉醒控制。因此，我们研究了表达食欲素的神经元是否参与雄性小鼠应激恢复力的调节。我们发现，在习得性无助测试（LHT）中，易感小鼠和恢复力强的小鼠的c-fos表达水平存在显著差异。此外，激活食欲素能神经元可使易感组产生恢复力，并且在其他行为测试中也持续观察到这种恢复力。然而，在诱导期（不可逃避应激暴露期间）激活食欲素能神经元对逃避测试中的应激恢复力没有影响。此外，使用通路特异性光刺激的分析表明，仅激活向伏隔核（NAc）内侧部分的食欲素能投射可介导焦虑减轻，但不足以在LHT中诱导恢复力。总体而言，我们的数据表明，向多个靶点的食欲素能投射可控制对各种应激源作出反应的多样且灵活的应激相关行为。
