多巴胺能球周细胞通过抑制外丛状细胞调节小鼠嗅球的信号输出
发布时间：2018-11-06 14:21
【摘要】：目的:多巴胺是中枢神经系统内一种重要的神经递质,发挥很多重要的生理功能,如对认知活动和运动功能的调控等。对帕金森病患者早期临床研究表明,脑内多巴胺水平也与嗅觉功能有关。研究多巴胺在嗅觉信息处理中所起的作用可能对探索神经退行性疾病的发病机制和早期诊断有一定的临床意义。本文的主要目的是探索嗅球中多巴胺能球周细胞在嗅球内部神经环路和嗅觉功能中的作用。方法:通过免疫荧光染色观察多巴胺能球周细胞在嗅球中的分布;通过脑立体定位注射,将ChR2-mCherry重组腺相关病毒注射到转基因小鼠的嗅小球层,待2-3周后病毒稳定表达,用振动切片机制备300μm厚度的嗅球离体脑片进行膜片钳记录,观察给予488nm激光刺激时嗅球内不同类型细胞的反应。注射病毒使多巴胺能球周细胞表达hM3Dq,腹腔注射CNO观察特异性激活多巴胺能球周细胞对于小鼠气味反应的影响。注射病毒使多巴胺能球周细胞表达DTR,腹腔注射DT观察特异性损伤多巴胺能球周细胞对于小鼠气味反应的影响。结果:多巴胺能球周细胞同时表达TH和GAD67。表达ChR2-mCherry的多巴胺能球周细胞在光刺激下可产生动作电位;给予嗅球脑片光刺激兴奋多巴胺能球周细胞后,可在外丛状细胞上记录到外向电流和超极化反应,这一外向电流可被GABA受体的拮抗剂阻断。结论:多巴胺能球周细胞可以共释放多巴胺和GABA,这些细胞通过释放GABA神经递质作用于周围的外丛状细胞,引起该类细胞的抑制反应,从而调节外丛状细胞的信号输出。多巴胺能球周细胞对外丛状细胞的调节在嗅球信息处理中发挥重要作用,并可能因此影响到动物的气味检测能力。
[Abstract]:Objective: dopamine (DA) is an important neurotransmitter in the central nervous system (CNS), which plays many important physiological functions, such as the regulation of cognitive activity and motor function. Early clinical studies in patients with Parkinson's disease have shown that brain dopamine levels are also associated with olfactory function. The study of the role of dopamine in olfactory information processing may be of clinical significance in exploring the pathogenesis and early diagnosis of neurodegenerative diseases. The main purpose of this paper is to explore the role of dopaminergic periglobule cells in the olfactory bulb in the internal loop of the olfactory bulb and olfactory function. Methods: the distribution of dopaminergic periglobular cells in olfactory bulb was observed by immunofluorescence staining. The ChR2-mCherry recombinant adeno-associated virus was injected into the olfactory bulb layer of transgenic mice by stereotactic injection. After 2-3 weeks, the virus was stably expressed. The isolated brain slices with 300 渭 m thickness olfactory bulb were prepared by vibration slicer for patch-clamp recording. To observe the response of different types of cells in olfactory bulb stimulated by 488nm laser. HM3Dq, was injected intraperitoneally to observe the effect of specific activation of dopaminergic globular cells on the odour response of mice. DTR, was injected intraperitoneally to observe the effect of specific injury of dopaminergic periglobular cells on the odour response of mice. Results: dopaminergic periglobular cells expressed both TH and GAD67. at the same time. Dopaminergic perispherical cells expressing ChR2-mCherry can produce action potential under photostimulation. After stimulation of dopaminergic periglandular cells with olfactory bulb slices, outward currents and hyperpolarizations were recorded in the outer plexiform cells, which could be blocked by the antagonist of GABA receptor. Conclusion: dopaminergic globular cells can co-release dopamine and GABA, by releasing GABA neurotransmitters acting on the outer plexiform cells, which can induce the inhibitory response of these cells and thus regulate the signal output of the outer plexiform cells. The regulation of peripheral bundles of dopaminergic cells plays an important role in the processing of olfactory bulb information, which may affect the ability of odor detection in animals.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R741
本文编号：2314536
[Abstract]:Objective: dopamine (DA) is an important neurotransmitter in the central nervous system (CNS), which plays many important physiological functions, such as the regulation of cognitive activity and motor function. Early clinical studies in patients with Parkinson's disease have shown that brain dopamine levels are also associated with olfactory function. The study of the role of dopamine in olfactory information processing may be of clinical significance in exploring the pathogenesis and early diagnosis of neurodegenerative diseases. The main purpose of this paper is to explore the role of dopaminergic periglobule cells in the olfactory bulb in the internal loop of the olfactory bulb and olfactory function. Methods: the distribution of dopaminergic periglobular cells in olfactory bulb was observed by immunofluorescence staining. The ChR2-mCherry recombinant adeno-associated virus was injected into the olfactory bulb layer of transgenic mice by stereotactic injection. After 2-3 weeks, the virus was stably expressed. The isolated brain slices with 300 渭 m thickness olfactory bulb were prepared by vibration slicer for patch-clamp recording. To observe the response of different types of cells in olfactory bulb stimulated by 488nm laser. HM3Dq, was injected intraperitoneally to observe the effect of specific activation of dopaminergic globular cells on the odour response of mice. DTR, was injected intraperitoneally to observe the effect of specific injury of dopaminergic periglobular cells on the odour response of mice. Results: dopaminergic periglobular cells expressed both TH and GAD67. at the same time. Dopaminergic perispherical cells expressing ChR2-mCherry can produce action potential under photostimulation. After stimulation of dopaminergic periglandular cells with olfactory bulb slices, outward currents and hyperpolarizations were recorded in the outer plexiform cells, which could be blocked by the antagonist of GABA receptor. Conclusion: dopaminergic globular cells can co-release dopamine and GABA, by releasing GABA neurotransmitters acting on the outer plexiform cells, which can induce the inhibitory response of these cells and thus regulate the signal output of the outer plexiform cells. The regulation of peripheral bundles of dopaminergic cells plays an important role in the processing of olfactory bulb information, which may affect the ability of odor detection in animals.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R741
【参考文献】
相关期刊论文 前2条
1 谭洁;罗敏敏;;嗅球对嗅觉信息的处理[J];生物物理学报;2010年03期
2 李凡,舒斯云,包新民;多巴胺受体的结构和功能[J];中国神经科学杂志;2003年06期
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