Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania.
Int J Neuropsychopharmacol. 2017 Oct 1;20(10):855-860. doi: 10.1093/ijnp/pyx054.
The ventral subiculum is known to be activated by the presentation of novel stressors. It has been hypothesized that neuronal ensembles at the ventral aspect of the hippocampal formation are involved in context-dependent processing and can guide the learning of appropriate action selections in response to threatening contexts. Artificial activation of the ventral subiculum can excite medium spiny neurons of the nucleus accumbens and can increase the excitability of mesolimbic dopamine neurons via a polysynaptic pathway through the basal ganglia. However, it remains unknown whether this circuit can be activated by aversive experience, and if so, whether ventral subiculum engages nucleus accumbens monosynaptically.
To address this, the retrograde tracer fluorogold was used in rats to label neurons projecting to the caudomedial nucleus accumbens. One to 2 weeks later, the same rats were exposed to psychogenic stress (i.e., acute restraint in a novel test room) or served as nonhandled controls, followed by dual immunocytochemical localization of retrogradely transported tracer and nuclear Fos.
Compared with controls, rats exposed to psychogenic stress displayed more fluorogold-positive ventral subiculum neurons that were double-labeled for Fos.
This study establishes that the direct pathway from ventral subiculum to the caudomedial nucleus accumbens is activated by stressful experience.
已知腹侧下托被新出现的应激源激活。有人假设,海马结构腹侧的神经元集合参与了上下文相关的处理,并能指导学习在威胁性环境下做出适当的行为选择。人工激活腹侧下托可以兴奋伏隔核的中间神经元,并通过基底神经节的多突触途径增加中脑边缘多巴胺神经元的兴奋性。然而,目前尚不清楚这个回路是否可以被厌恶经验激活,如果可以,腹侧下托是否通过单突触与伏隔核连接。
为了解决这个问题,我们在大鼠中使用逆行示踪剂氟金来标记投射到尾侧中隔核伏隔核的神经元。1 到 2 周后,同一批大鼠接受精神性应激(即在新的测试室中急性束缚)或作为未处理的对照,然后进行逆行转运示踪剂和核 Fos 的双重免疫细胞化学定位。
与对照组相比,暴露于精神性应激的大鼠显示出更多的腹侧下托氟金阳性神经元,这些神经元同时表达 Fos。
这项研究表明,腹侧下托到尾侧中隔核伏隔核的直接通路是被应激经验激活的。