Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, London, United Kingdom.
Elife. 2024 Jun 28;12:RP90278. doi: 10.7554/eLife.90278.
Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor comorbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline (NA) reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both NA and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.
帕金森病（PD）的特征是黑质致密部多巴胺神经元退化引起的运动障碍。除了这些症状，PD 患者还经常患有非运动性合并症，包括睡眠和精神障碍，这些被认为依赖于 5-羟色胺能和去甲肾上腺素能传递的伴随改变。5-羟色胺能神经元的主要部位是中缝背核（DRN），提供全脑 5-羟色胺能输入。在这里，我们确定了电生理和形态学参数，以在对照条件下和纹状体注射儿茶酚胺毒素 6-羟多巴胺（6-OHDA）后在小鼠 DRN 中对 5-羟色胺能和多巴胺能神经元进行分类。6-OHDA 改变了这两种神经元群体的电和形态特性。在 5-羟色胺能神经元中，当 6-OHDA 与去甲肾上腺素（NA）再摄取抑制剂去甲丙咪嗪联合注射时，大多数变化都会逆转，从而保护 NA 末梢。我们的结果表明，6-OHDA 小鼠模型中 NA 和多巴胺的耗竭导致 DRN 神经回路发生变化。
