Partial depletion of dopaminergic neurons in the substantia nigra impairs olfaction and alters neural activity in the olfactory bulb
Partial depletion of dopaminergic neurons in the substantia nigra impairs olfaction and alters neural activity in the olfactory bulb
复制标题
黑质中多巴胺能神经元的部分耗尽会损害嗅觉并改变嗅球的神经活动
DOI：
10.1038/s41598-018-36538-2
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发表时间：
2019
影响因子：
4.6
通讯作者：
Li Anan
中科院分区：
文献类型：
--
作者：
Zhang Wenfeng;Sun Changcheng;Shao Yufeng;Zhou Zheng;Hou Yiping;Li Anan
嗅觉障碍是帕金森病(PD)早期出现的一种主要的非运动症状，帕金森病是一种以黑质多巴胺能神经元丢失为特征的神经退行性疾病。6-羟基多巴胺(6-OHDA)耗竭黑质多巴胺能神经元被广泛用作帕金森病的模型，最终导致运动障碍。然而，在运动缺陷出现之前，嗅觉行为以及更重要的是嗅球(OB)的神经活动是否受到损害，目前还很不清楚。我们通过注射6-OHDA部分耗尽了小鼠黑质多巴胺能群。注射6-OHDA 7天后，运动能力无明显变化，但嗅觉驱动行为明显受损。在黑质内注射6-OHDA可显著增加所有频段OB正在进行的局部场电位的功率，并降低气味诱发的兴奋性β反应和抑制性高伽马反应。此外，6-OHDA处理导致清醒小鼠OB的二尖瓣细胞对气味诱发的钙反应增加。这些数据表明，黑质多巴胺能群枯竭引起的嗅觉障碍可能是由于OB内二尖瓣细胞异常活跃所致。
Olfactory dysfunction is a major non-motor symptom that appears during the early stages of Parkinson’s Disease (PD), a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra (SN). Depletion of SN dopaminergic neurons by 6-hydroxydopamine (6-OHDA) is widely used as a model for PD and ultimately results in motor deficits. However, it is largely unknown whether olfactory behavior and, more importantly, neural activity in the olfactory bulb (OB) are impaired prior to the appearance of motor deficits. We partially depleted the SN dopaminergic population in mice by injection of 6-OHDA. Seven days after injection of 6-OHDA, motor ability was unchanged but olfactory-driven behaviors were significantly impaired. Injection of 6-OHDA into the SN significantly increased the power of the ongoing local field potential in the OB for all frequency bands, and decreased odor-evoked excitatory beta responses and inhibitory high-gamma responses. Moreover, 6-OHDA treatment led to increased odor-evoked calcium responses in the mitral cells in the OB of awake mice. These data suggest that the olfactory deficits caused by depletion of the SN dopaminergic population are likely due to abnormal hyperactivity of the mitral cells in the OB.