Company Verónica, Andreu-Cervera Abraham, Madrigal M Pilar, Andrés Belén, Almagro-García Francisca, Chédotal Alain, López-Bendito Guillermina, Martinez Salvador, Echevarría Diego, Moreno-Bravo Juan A, Puelles Eduardo
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, Spain.
Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.
Front Cell Dev Biol. 2021 Jun 8;9:682067. doi: 10.3389/fcell.2021.682067. eCollection 2021.
The fasciculus retroflexus is an important fascicle that mediates reward-related behaviors and is associated with different psychiatric diseases. It is the main habenular efference and constitutes a link between forebrain regions, the midbrain, and the rostral hindbrain. The proper functional organization of habenular circuitry requires complex molecular programs to control the wiring of the habenula during development. However, the mechanisms guiding the habenular axons toward their targets remain mostly unknown. Here, we demonstrate the role of the mesodiencephalic dopaminergic neurons (substantia nigra pars compacta and ventral tegmental area) as an intermediate target for the correct medial habenular axons navigation along the anteroposterior axis. These neuronal populations are distributed along the anteroposterior trajectory of these axons in the mesodiencephalic basal plate. Using and experiments, we determined that this navigation is the result of attraction generated by the mesodiencephalic dopaminergic neurons. This attraction is mediated by the receptor deleted in colorectal cancer (DCC), which is strongly expressed in the medial habenular axons. The increment in our knowledge on the fasciculus retroflexus trajectory guidance mechanisms opens the possibility of analyzing if its alteration in mental health patients could account for some of their symptoms.
缰核脚间束是一条重要的纤维束,介导与奖赏相关的行为,且与多种精神疾病有关。它是主要的缰核传出纤维,构成了前脑区域、中脑和延髓前部之间的联系。缰核神经回路的正常功能组织需要复杂的分子程序来在发育过程中控制缰核的神经连接。然而,引导缰核轴突到达其靶标的机制大多仍不清楚。在这里,我们证明了中脑多巴胺能神经元(黑质致密部和腹侧被盖区)作为内侧缰核轴突沿前后轴正确导航的中间靶标的作用。这些神经元群体沿着中脑基板中这些轴突的前后轨迹分布。通过[具体实验方法1]和[具体实验方法2]实验,我们确定这种导航是由中脑多巴胺能神经元产生的[某种吸引作用]的结果。这种吸引作用由在结直肠癌中缺失的受体(DCC)介导,该受体在缰核内侧轴突中强烈表达。我们对缰核脚间束轨迹引导机制的认识的增加,开启了分析精神疾病患者中其改变是否可解释其某些症状的可能性。