University Department of Pharmacology, Oxford, OX1 3QT, UK.
Neuroscience. 2011 Jul 14;186:135-45. doi: 10.1016/j.neuroscience.2011.04.004. Epub 2011 Apr 14.
High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is an established neurosurgical therapy for movement disability in advanced Parkinson's disease (PD), but some patients experience psychiatric side-effects like depression. In a previous electrophysiological study, we observed that HFS of the STN inhibited a population of neurones in the rat dorsal raphe nucleus (DRN), with firing properties characteristic of 5-HT neurones. The present study extended these findings to a second population of neurones, and combined extracellular recording with juxtacellular-labelling to investigate the chemical identity of the neurones affected by HFS. Bilateral HFS (130 Hz, 100-200 μA, 5 min) of the STN inhibited (26.0±2.9%) the firing of 37/74 DRN neurones displaying a slow, regular firing pattern. Slower firing neurones were more strongly inhibited than those firing faster. Importantly, 10 inhibited DRN neurones were juxtacellular-labelled with neurobiotin, and all neurones contained 5-HT as shown by post-mortem 5-HT immunocytochemistry. A minority of slow firing DRN neurones (18/74) were activated by STN HFS (37.9±8.3%) which was not observed previously. Of these neurones, three were juxtacellular-labelled and one was 5-HT immunopositive. Also a small number of DRN neurones (19/74) did not respond to HFS, four of which were juxtacellular-labelled and all contained 5-HT. These data show that individual chemically-identified 5-HT-containing neurones in the DRN were modulated by STN HFS, and that the majority were inhibited but some were activated and some failed to respond. These data extend previous findings of modulation of the 5-HT system by STN HFS but suggest a destabilisation of the 5-HT system rather than simple inhibition as indicated previously. Although the mechanism is not yet known, such changes may contribute to the psychiatric side-effects of STN stimulation in some PD patients.
高频刺激（HFS）丘脑底核（STN）是治疗晚期帕金森病（PD）运动障碍的一种既定神经外科疗法，但一些患者会出现抑郁等精神副作用。在之前的一项电生理研究中，我们观察到 HFS 抑制了大鼠背侧中缝核（DRN）中的一群神经元，其放电特性具有 5-HT 神经元的特征。本研究将这些发现扩展到第二群神经元，并结合细胞外记录和细胞内标记来研究受 HFS 影响的神经元的化学特性。双侧 STN 的 HFS（130 Hz，100-200 μA，5 分钟）抑制了 74 个 DRN 神经元中的 37 个（26.0±2.9%），这些神经元显示出缓慢、规则的放电模式。较慢放电的神经元比较快放电的神经元受到更强的抑制。重要的是，10 个被抑制的 DRN 神经元被神经生物素进行了细胞内标记，所有神经元都含有 5-HT，这一点通过死后的 5-HT 免疫细胞化学显示出来。少数慢放电 DRN 神经元（18/74）被 STN HFS 激活（37.9±8.3%），这是以前没有观察到的。其中三个神经元被细胞内标记，一个神经元是 5-HT 免疫阳性的。同样，一小部分 DRN 神经元（19/74）对 HFS 没有反应，其中四个神经元被细胞内标记，所有神经元都含有 5-HT。这些数据表明，DRN 中单个化学鉴定的含有 5-HT 的神经元被 STN HFS 调制，大多数被抑制，但有些被激活，有些则没有反应。这些数据扩展了之前 STN HFS 调制 5-HT 系统的发现，但表明 5-HT 系统不稳定，而不是之前表明的简单抑制。尽管其机制尚不清楚，但这些变化可能会导致一些 PD 患者 STN 刺激的精神副作用。
