Xu Chunpeng, Sun Yanfei, Cai Xuewei, You Tingting, Zhao Hongzhe, Li Yang, Zhao Hua
Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China.
Front Behav Neurosci. 2018 Oct 9;12:238. doi: 10.3389/fnbeh.2018.00238. eCollection 2018.
The habenula is a nuclear complex composed of the lateral habenula (LHb) and medial habenula (MHb), two distinct structures. Much progress has been made to emphasize the role of the LHb in the pathogenesis of depression. In contrast, relatively less research has focused on the MHb. However, in recent years, the role of the MHb has begun to gain increasing attention. The MHb connects to the interpeduncular nucleus (IPN) both morphologically and functionally. The MHb-IPN pathway plays an important role in regulating higher brain functions, including cognition, reward, and decision making. It indicates a role of the MHb in the pathogenesis of depression. Thus, we investigated the role of the MHb-IPN pathway in depression. MHb metabolic activity was increased in the chronic unpredictable mild stress (CUMS)-exposed rat model of depression. MHb lesions in the CUMS-exposed rats reversed anhedonia-like behavior, as observed in the sucrose preference test, and significantly downregulated the elevated metabolic activity of the IPN. Substance P (SP)-containing neurons of the MHb were found to innervate the IPN and to be the main source of SP in the IPN. SP content of IPN tissue of the CUMS-exposed rats was increased and MHb lesions reversed this change. In the experiment, firing rate recordings showed that SP perfusion increased the activity of IPN neurons. Our results suggest that hyperactivity of the MHb-IPN circuit is involved in the anhedonia-like behavior of depression, and that SP mediates the effect of the MHb on IPN neurons.
缰核是一个由外侧缰核（LHb）和内侧缰核（MHb）组成的核复合体，二者为不同的结构。在强调LHb在抑郁症发病机制中的作用方面已取得了很大进展。相比之下，对MHb的研究相对较少。然而，近年来，MHb的作用开始受到越来越多的关注。MHb在形态和功能上均与脚间核（IPN）相连。MHb-IPN通路在调节包括认知、奖赏和决策在内的高级脑功能中起重要作用。这表明MHb在抑郁症发病机制中发挥作用。因此，我们研究了MHb-IPN通路在抑郁症中的作用。在慢性不可预测轻度应激（CUMS）诱导的抑郁症大鼠模型中，MHb的代谢活性增加。在CUMS诱导的大鼠中，MHb损伤逆转了蔗糖偏好试验中观察到的快感缺失样行为，并显著下调了IPN升高的代谢活性。发现MHb中含P物质（SP）的神经元支配IPN，并且是IPN中SP的主要来源。CUMS诱导大鼠的IPN组织中SP含量增加，而MHb损伤逆转了这一变化。在实验中，放电频率记录显示SP灌注增加了IPN神经元的活性。我们的结果表明，MHb-IPN回路的过度活跃与抑郁症的快感缺失样行为有关，并且SP介导了MHb对IPN神经元的作用。
