【作者】 陈波；

【导师】 周逸峰；

【作者基本信息】 中国科学技术大学 ， 生物物理学， 2010， 博士

【摘要】 很多生理学与行为学的研究都表明酒精对很多视觉功能,如视锐度、对比敏感度、运动知觉等都有不同程度的影响,但是酒精产生这些影响的生理机制还不是完全清楚。初级视皮层神经元的反应特性是视觉信息处理与整合的重要生理基础。大部分的初级视皮层神经元会对刺激图形的某方面属性具有选择性反应,深入研究酒精对初级视皮层神经元反应特性的影响对了解酒精影响视知觉的生理机制具有重要意义。本工作采用在体胞外单细胞记录的方法,研究了急性酒精暴露对猫初级视皮层(17区)神经元多种反应特性的影响,主要包括：1.急性酒精暴露对猫17区神经元自发发放,视觉刺激诱发反应及信噪比的影响神经元的自发发放为神经元在没有受到视觉刺激情况下的发放情况,代表神经元在静息状态下的活动水平。诱发反应则体现了神经元对视觉刺激的响应情况。信噪比为最大诱发反应与自发反应的比值,可以反映出神经元在背景噪音中提取信号能力的强弱。我们研究了急性酒精暴露对猫初级视皮层神经元的自发发放,视觉刺激诱发反应及信噪比的影响。结果发现：低浓度酒精下,神经元的这些反应特性均没有受到显著影响。较高浓度的酒精可以导致神经元自发发放,诱发发放与信噪比的显著下降。我们认为这种信噪比的下降是由于最大诱发发放(即峰值发放)比自发发放降低更多而导致的。信噪比的下降意味着神经元从背景噪音中提取信号的能力的减弱,因而可能是酒精减缓视觉信息传递速度的原因之一。2.急性酒精暴露对猫17区神经元的方位选择性及方向选择性的影响初级视皮层神经元的方位选择性与方向选择性指对具有不同朝向(方位)及不同运动方向的刺激具有选择性的反应,在物体的形状识别与运动识别中具有重要的作用。我们发现,在较高浓度下,急性酒精暴露导致神经元的方位偏爱指数显著下降,而且这种方位偏爱指数的下降是方位调谐曲线的波宽与垂直最优方位反应比共同变化的结果。酒精对神经元的方向选择性强度整体上没有显著性影响,但是具有较强方向选择性的神经元在急性酒精暴露后出现方向偏爱指数的显著降低。我们还发现神经元的最优方位与最优方向在急性酒精暴露后发生了一定的偏移。低浓度酒精对神经元的这些反应特性没有显著影响。我们认为神经元的这些反应特性的变化主要是由于酒精减弱了皮层中的兴奋性系统的作用而引起的。我们的研究结果为酒精影响形状识别与运动识别能力等行为学研究结果提供了可能的生理基础。3.急性酒精暴露对猫17区神经元空间频率选择性的影响神经元的空间频率选择性指对不同空间频率的视觉刺激的选择性反应,在对物体空间特性的认知中具有重要作用。我们的研究结果显示酒精对神经元的最优空间频率没有显著影响,但是急性酒精暴露导致猫17区神经元的空间频率选择性在整体上降低。进一步的分析表明,酒精对神经元空间频率选择性的影响与神经元自身的最优空间频率也有一定的相关性,最优空间频率较高的神经元的空间频率选择性受酒精的影响相对较大。从兴奋型与抑制性的作用角度来看,初级视皮层神经元的空间频率选择性的机制与方位选择性的机制具有一定的相似性,因此,我们推测酒精对神经元空间频率选择性的影响也主要是由于酒精对皮层内兴奋性系统的抑制而导致的。这些结果为酒精对空间视觉很多方面的损害提供了可能的生理学解释。结论：急性酒精暴露可以影响猫初级视皮层神经元的自发发放、视觉刺激诱发反应、方位及方向选择性与空间频率选择性。酒精对皮层内兴奋性系统的抑制作用所引起的神经元对最优刺激的反应降低可能是导致这些结果的主要原因。我们的研究结果一定程度上为行为学研究中所发现的与酒精相关的很多视觉功能的下降提供了可能的神经机制。更多还原

【Abstract】 Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation-and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion, while spatial response properties are thought to play an important role in many aspects of spatial vision. Thus, investigation on the effect of alcohol to the response properties of primary visual cortex (A 17) neurons could help us better understanding the psycophysical mechanism mediating many aspects of alcohol-induced changes observed in behavioral studies.In this experiment, we used the extracellular single-unit recording technique to examine the response properties of neurons in A17 neurons of adult cats.1.The effect of acute alcohol exposure on the spontaneous activity, visual evoked unit resonse and the signal-to-noise ratio of A17 neuronsThe spontaneous activity and visual evoked response reflect the neuronal activity with and without visual stimuli; while the signal-to-noise ratio indicates the ability of the cell to retrieve signals from noisy backgrounds.We found that acute administration of alcohol results in decreased stimulus driven and spontaneous activity. The proportionally greater decrease in peak response resulted in a reduced signal-to-noise ratio, indicating a reduced signaling capacity of A17 cells in general, which may be partially involved in the impaired information processing after the administration of alcohol.2.The effect of acute alcohol exposure on the orientation selectivity and direction selectivity of A17 neuronsOrientation selectivity and direction selectivity, which refer to the selective response to both the angular orientation and the direction of motion of lines, bars, and edges, are fundamental properties of most neurons in the primary visual cortex and are thought to participate in the perception of form and motion. We found that high concentration alcohol reduces the orientation selectivity of A17 cells. In addition, our results suggest that the changes of orientation selectivity during the administration of alcohol were due to the changes in both bandwidth and orthogonal/optimal responses. The direction selectivity for the whole population exhibited a tendency of decreased selectivity, however, did not approach the statistical significance. The direction selelctivity of strongly direction selective neurons was significantly reduced after acute alcohol administration. Detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were also observed after acute alcohol administration.Our results suggest that despite the effect of the enhanced GABA-mediated inhibition, the decreased excitatory input from LGN and/or other cortical cells may have a major role in reducing the orientation selectivity of A17 neurons in overall. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.3.The effect of acute alcohol on the spatial properties of A17 neuronsThe detection of repetitive patterns such as gratings may be achieved by neurons which selectively sensitive to a limited band of spatial frequencies. The spatial frequency selectivity of cortical cell is thought to play an important role in many aspects of spatial vision. In this experiment, we found that alcohol could significantly decrease the spatial frequency selectivity A17 neurons. No significant changes were observed in optimal spatial frequency after acute alcohol exposure. Moreover, the cells that had relatively higher optimal spatial frequencies were more severely affected by alcohol than that had relatively lower optimal spatial frequencies. Considering that the origin of cortical spatial frequency selectivity involves a mechanism similar to that of orientation selectivity in terms of the balance of excitation and inhibition, the predominant mechanism mediating such changes could alco be attributed to the alcohol-induced reduction of the excitotary neurotransmitter system. Our results suggest an additional mechanism by which alcohol impaired some aspects of spatial vision.Conclusion:Acute alcohol exposure could alter the spontaneous, visually evoked response, orientation/direction selectivity and spatial frequency selectivity of A17 neurons. The reduced response to the optimal stimulus may play an important role in mediating such changes. Our research may provide a possible physiological explanation for the alcohol-related deficits in many aspects of visual function observed in behavioral studies.更多还原