Department of Neuroscience, Maastricht University, The Netherlands.
J Psychiatr Res. 2011 Oct;45(10):1307-15. doi: 10.1016/j.jpsychires.2011.04.011. Epub 2011 Jun 8.
High frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced Parkinson's disease, but this treatment can elicit disabling mood changes. Our recent experiments show that in rats, HFS of the STN both inhibits the firing of 5-HT (5-hydroxytryptamine; serotonin) neurons in the dorsal raphe nucleus (DRN) and elicits 5-HT-dependent behavioral effects. The neural circuitry underpinning these effects is unknown. Here we investigated in the dopamine-denervated rat the effect of bilateral HFS of the STN on markers of neuronal activity in the DRN as well as DRN input regions. Controls were sham-stimulated rats. HFS of the STN elicited changes in two 5-HT-sensitive behavioral tests. Specifically, HFS increased immobility in the forced swim test and increased interaction in a social interaction task. HFS of the STN at the same stimulation parameters, increased c-fos immunoreactivity in the DRN, and decreased cytochrome C oxidase activity in this region. The increase in c-fos immunoreactivity occurred in DRN neurons immunopositive for the GABA marker parvalbumin. HFS of the STN also increased the number of c-fos immunoreactive cells in the lateral habenula nucleus, medial prefrontal cortex but not significantly in the substantia nigra. Collectively, these findings support a role for circuitry involving DRN GABA neurons, as well as DRN afferents from the lateral habenula nucleus and medial prefrontal cortex, in the mood effects of HFS of the STN.
高频刺激（HFS）丘脑底核（STN）是治疗晚期帕金森病患者运动功能障碍的神经外科治疗选择，但这种治疗会引起致残的情绪变化。我们最近的实验表明，在大鼠中，STN 的 HFS 既抑制中缝背核（DRN）中 5-HT（5-羟色胺；血清素）神经元的放电，又引发 5-HT 依赖性行为效应。这些效应的神经回路尚不清楚。在这里，我们在多巴胺耗竭大鼠中研究了双侧 STN 的 HFS 对 DRN 中神经元活动标志物以及 DRN 输入区域的影响。对照组为假刺激大鼠。STN 的 HFS 引起了两种 5-HT 敏感行为测试的变化。具体来说，HFS 增加了强迫游泳试验中的不动性，并增加了社交互动任务中的互动。在相同的刺激参数下，STN 的 HFS 增加了 DRN 中的 c-fos 免疫反应性，并降低了该区域的细胞色素 C 氧化酶活性。c-fos 免疫反应性的增加发生在免疫阳性 GABA 标志物 parvalbumin 的 DRN 神经元中。STN 的 HFS 还增加了外侧缰核、内侧前额叶皮质中 c-fos 免疫反应性细胞的数量，但在黑质中没有显著增加。总之，这些发现支持涉及 DRN GABA 神经元以及来自外侧缰核和内侧前额叶皮质的 DRN 传入的回路在 STN 的 HFS 的情绪效应中的作用。
