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多巴胺能球周細胞通過抑制外叢狀細胞調(diào)節(jié)小鼠嗅球的信號輸出

發(fā)布時間:2018-11-06 14:21
【摘要】:目的:多巴胺是中樞神經(jīng)系統(tǒng)內(nèi)一種重要的神經(jīng)遞質(zhì),發(fā)揮很多重要的生理功能,如對認知活動和運動功能的調(diào)控等。對帕金森病患者早期臨床研究表明,腦內(nèi)多巴胺水平也與嗅覺功能有關(guān)。研究多巴胺在嗅覺信息處理中所起的作用可能對探索神經(jīng)退行性疾病的發(fā)病機制和早期診斷有一定的臨床意義。本文的主要目的是探索嗅球中多巴胺能球周細胞在嗅球內(nèi)部神經(jīng)環(huán)路和嗅覺功能中的作用。方法:通過免疫熒光染色觀察多巴胺能球周細胞在嗅球中的分布;通過腦立體定位注射,將ChR2-mCherry重組腺相關(guān)病毒注射到轉(zhuǎn)基因小鼠的嗅小球?qū)?待2-3周后病毒穩(wěn)定表達,用振動切片機制備300μm厚度的嗅球離體腦片進行膜片鉗記錄,觀察給予488nm激光刺激時嗅球內(nèi)不同類型細胞的反應(yīng)。注射病毒使多巴胺能球周細胞表達hM3Dq,腹腔注射CNO觀察特異性激活多巴胺能球周細胞對于小鼠氣味反應(yīng)的影響。注射病毒使多巴胺能球周細胞表達DTR,腹腔注射DT觀察特異性損傷多巴胺能球周細胞對于小鼠氣味反應(yīng)的影響。結(jié)果:多巴胺能球周細胞同時表達TH和GAD67。表達ChR2-mCherry的多巴胺能球周細胞在光刺激下可產(chǎn)生動作電位;給予嗅球腦片光刺激興奮多巴胺能球周細胞后,可在外叢狀細胞上記錄到外向電流和超極化反應(yīng),這一外向電流可被GABA受體的拮抗劑阻斷。結(jié)論:多巴胺能球周細胞可以共釋放多巴胺和GABA,這些細胞通過釋放GABA神經(jīng)遞質(zhì)作用于周圍的外叢狀細胞,引起該類細胞的抑制反應(yīng),從而調(diào)節(jié)外叢狀細胞的信號輸出。多巴胺能球周細胞對外叢狀細胞的調(diào)節(jié)在嗅球信息處理中發(fā)揮重要作用,并可能因此影響到動物的氣味檢測能力。
[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.
【學(xué)位授予單位】:桂林醫(yī)學(xué)院
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R741

【參考文獻】

相關(guān)期刊論文 前2條

1 譚潔;羅敏敏;;嗅球?qū)π嵊X信息的處理[J];生物物理學(xué)報;2010年03期

2 李凡,舒斯云,包新民;多巴胺受體的結(jié)構(gòu)和功能[J];中國神經(jīng)科學(xué)雜志;2003年06期

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