GABA能改善慢性吗啡暴露猫初级视皮层功能

发布时间：2018-05-17 19:08

本文选题：初级视皮层 + 方位选择性　；参考：《中国科学技术大学》2010年博士论文

【摘要】：药物滥用是当今世界性的重要社会和医学问题。长期使用阿片类药物不仅会导致生理和心理上的依赖,也会导致脑功能的损伤。前人的结果提示,慢性吗啡暴露会导致猫初级视皮层(17区)反应调制能力的退化,包括自发反应的升高,信噪比的下降,方位选择性和方向选择性的弱化,以及反应时程的延长。另一方面,也有其他结果表明,慢性吗啡暴露也会使GABA(?)系统受到损伤。 GABA能系统是皮层内重要的抑制能系统之一。前人的一些结果提示,来自GABA能系统的抑制,对视觉功能包括方向、方位选择性的形成等发挥重要的调节作用。同时,对缺乏抑制的神经元补充抑制,可以改善它们的功能。而慢性吗啡暴露猫皮层细胞反应调制能力的退化,很有可能是由于来自于GABA能系统的抑制水平的衰减所导致的。因此,我们考虑补充抑制是否可以恢复由慢性吗啡暴露引起的17区细胞的损伤。如果可以,那我们就可以证实前面的假说：慢性吗啡暴露猫视觉的退化,确实部分由于来自GABA能系统的抑制水平的衰减所导致。为了检验这一假设,我们在吗啡暴露组猫和作为对照的盐水处理组猫中,使用多管微电极对17区细胞分别微电泳GABA以及GABAA受体的拮抗剂荷包牡丹碱,检测其对细胞的影响。我们分别在给药前和给药后检测了2组猫17区细胞的自发反应、信噪比、方位选择性和方向选择性。我们的实验结果表明,对于吗啡暴露猫17区细胞补充施加GABA,能够改善其视觉功能。GABA的施加,可以减低自发反应的幅度,升高对视觉刺激信号的分辨能力,改善方位选择性和方向选择性。在施加GABA之后,某些吗啡暴露组猫中的17区细胞甚至表现出和盐水对照组猫的细胞类似的反应。而另一方面,荷包牡丹碱的施加则使得盐水对照组的细胞的反应调制表现出了退化现象。同时,荷包牡丹碱的施加对吗啡暴露组猫的细胞的影响比盐水对照组的要弱。相反地,GABA的施加对吗啡暴露组猫的细胞的影响则比盐水对照组的强。此外,对于吗啡暴露组已经有强选择性的细胞,GABA仍然能增强它们的方位选择性和方向选择性；而对于盐水对照组中的强选择性细胞,则没有这样的效果。这些结果证实了,在慢性吗啡暴露猫中,GABA调制的抑制确实发生了退化,也进一步的说明了,慢性吗啡暴露猫皮层细胞反应调制能力的退化确实是由于来源于GABA能系统的抑制退化所导致的。补充GABA能够改善吗啡暴露猫17区细胞的功能,修复吗啡暴露引起的损伤。因此,这一实验结果对药物滥用导致的感觉、运动和认知功能的损伤的治疗手段的改进,有着潜在的应用意义。
[Abstract]:Drug abuse is an important social and medical problem in the world. Long-term use of opioids leads not only to physical and psychological dependence, but also to brain dysfunction. The previous results suggest that chronic morphine exposure may degrade the modulation ability of the primary visual cortex in cats, including increased spontaneous response, decreased signal-to-noise ratio, weakened azimuth selectivity and directional selectivity. And the prolongation of the reaction time. On the other hand, there are other results indicating that chronic morphine exposure also causes GABA A) The system was damaged. GABA energy system is one of the important inhibitory energy systems in the cortex. Some previous results suggest that inhibition from GABA system plays an important role in regulating visual function including orientation and azimuth selectivity. At the same time, the supplement of inhibition to neurons lacking inhibition can improve their function. The degradation of the modulation ability of the cortical cells in the cats exposed to chronic morphine may be due to the attenuation of the inhibition level from the GABA energy system. Therefore, we consider whether supplemental inhibition can restore the damage of 17 region cells caused by chronic morphine exposure. If so, we can confirm the previous hypothesis that chronic morphine exposure to visual degeneration in cats is partly due to attenuated levels of inhibition from the GABA system. To test this hypothesis, we used multi-tube microelectrodes in morphine exposed cats and saline treated cats as control to detect the effects of microelectrophoretic GABA and bicuculline, an antagonist of GABAA receptor, on the cells in region 17, respectively. The spontaneous response, SNR, azimuth selectivity and directional selectivity were detected before and after administration of the drug in two groups of cats. Our results show that supplementation of GABA to the cells of area 17 of morphine exposed cats can improve their visual function. GABA can reduce the amplitude of spontaneous response and increase the resolution of visual stimulation signals. Improve azimuth selectivity and directional selectivity. After administration of GABA, the 17 region cells in some morphine exposed cats even showed similar responses to those of saline control cats. On the other hand, the application of bicuculline resulted in the degradation of cell response modulation in saline control group. At the same time, the effect of bicuculline on the cells of the cats exposed to morphine was weaker than that of the saline group. On the contrary, the effect of GABA on the cells of morphine exposed cats was stronger than that of saline control. In addition, GABA could enhance the orientation selectivity and directional selectivity of morphine exposed cells, but not in saline control group. These results confirm that the inhibition of GABA modulation does degrade in cats exposed to chronic morphine, and further explain, The degradation of the modulation ability of cortical cells in cats exposed to chronic morphine is due to the inhibition of degeneration by the GABA energy system. Supplementation of GABA can improve the function of area 17 cells exposed to morphine and repair the damage caused by morphine exposure. Therefore, the results of this experiment have potential application significance in improving the treatment of sensory, motor and cognitive impairment caused by drug abuse.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R363

【共引文献】