Aznar S, Qian Z-X, Knudsen G M
Neurobiology Research Unit 9201, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Neuroscience. 2004;124(3):573-81. doi: 10.1016/j.neuroscience.2003.12.020.
The median raphe nucleus is involved in controlling and maintaining hippocampal activity through its projection to inhibitory neurons in medial septum and hippocampus. It has been shown that anterogradely axonal-traced fibers originating in the median raphe nucleus project onto calbindin-containing neurons in hippocampus and parvalbumin-containing neurons in medial septum. Parallel immunohistochemistry studies showing serotonin fibers contacting calbindin- and parvalbumin-positive neurons have led to the assumption that raphe fibers projecting on these types of neurons are mainly serotonergic. However, in both dorsal and median raphe nucleus there is a large amount of non-serotonergic neurons which also are projecting neurons, indicating that a part of the raphe fibers projecting to hippocampus and septum may be non-serotonergic. Our aim was to determine whether there is a non-serotonergic projection from the raphe nucleus onto calbindin- and parvalbumin-containing neurons in hippocampus and septum. Biotin dextran amine was used as the anterograde neuronal tracer and injected into either dorsal or median raphe nucleus. By use of triple immunofluorescence-labeling we analyzed the serotonergic content of the biotin dextran amine-labeled fibers contacting parvalbumin- and calbindin-positive neurons. Surprisingly, we found a significant non-serotonergic projection from both dorsal and median raphe nuclei onto calbindin- and parvalbumin-containing interneurons in septum and hippocampus, with a preference in hippocampus for projecting onto calbindin-positive neurons. These results indicate that the raphe nuclei may exert their control on hippocampal and septal activity not only through a serotonergic projection, but also through a significant non-serotonergic pathway.
中缝正中核通过其向内侧隔区和海马中抑制性神经元的投射，参与控制和维持海马活动。研究表明，源自中缝正中核的顺行轴突追踪纤维投射到海马中含钙结合蛋白的神经元和内侧隔区中含小白蛋白的神经元上。平行免疫组织化学研究显示5-羟色胺纤维与钙结合蛋白和小白蛋白阳性神经元接触，这使得人们推测投射到这些类型神经元上的中缝纤维主要是5-羟色胺能的。然而，在背侧和中缝正中核中都有大量非5-羟色胺能神经元，它们也是投射神经元，这表明投射到海马和隔区的部分中缝纤维可能是非5-羟色胺能的。我们的目的是确定中缝核是否存在向海马和隔区中含钙结合蛋白和小白蛋白的神经元的非5-羟色胺能投射。生物素葡聚糖胺用作顺行神经元示踪剂，并注入背侧或中缝正中核。通过使用三重免疫荧光标记，我们分析了与小白蛋白和钙结合蛋白阳性神经元接触的生物素葡聚糖胺标记纤维的5-羟色胺能含量。令人惊讶的是，我们发现背侧和中缝正中核都向隔区和海马中含钙结合蛋白和小白蛋白的中间神经元发出了显著的非5-羟色胺能投射，在海马中更倾向于投射到钙结合蛋白阳性神经元上。这些结果表明，中缝核可能不仅通过5-羟色胺能投射，还通过一条显著的非5-羟色胺能途径来控制海马和隔区的活动。
