摘要
一.慢性吗啡暴露影响猫V1区神经元的对比度反应功能
迄今为止,阿片类药物滥用仍然是国际范围内一个重要的社会问题和严重的医学药物问题。长期的阿片滥用不仅会导致生理性和精神性依赖,也会造成神经系统损伤。由于阿片受体在哺乳动物的中枢神经系统中广泛分布,并且大量存在于视觉系统中,所以人们推测阿片可能会影响视觉系统的多方面功能。已有研究表明慢性吗啡暴露会导致视皮层发生显著的形态变化,会改变视皮层神经元的一些视觉反应特性,包括方向和方位选择性、反应调制特性以及反应潜伏期等。
图形对比度编码功能在视觉系统信息处理过程中起着非常重要的作用。视皮层神经元对视觉空间里的对比度参数特征有一定的反应特性。视觉信息对比度的变化不仅会影响人类对运动的感知,例如速度感知、方位方向辨别以及图形-背景分离等运动知觉,而且会影响到神经元调谐的一些参数,会导致空间频率和速度调谐曲线的改变。目前,关于慢性吗啡暴露对视皮层细胞对比度反应功能影响的研究还很缺乏。
本研究中,我们采用在体胞外单细胞记录的方法研究和比较了慢性吗啡暴露猫和盐水暴露猫(对照组)初级视皮层神经元的对比度反应功能。实验结果显示,这两组实验动物的C50(反应值为1/2饱和反应值时的对比度值)都是呈近似于正态分布并且这两组分布之间有着显著性差异。与盐水对照组C50分布(0.07-0.32)相比,慢性吗啡暴露组的C50分布范围更广(0.10-0.77)。吗啡组中有超过一半的细胞(51.3%,41of80)表现出低对比敏感度(C50≥0.3),而盐水对照组中只有7.0%的细胞(4of57)表现出相似的反应特性。另一方面,高对比敏感度(C50≤0.1)的细胞占盐水对照组细胞总数的8.8%(5of57),高于其占吗啡暴露组细胞总数的比例(2.5%,2of80)。因此,与对照组相比,慢性吗啡暴露组神经元的对比敏感度显著性下降。另外,我们还记录并分析了两组实验动物的所记录神经元的最大视觉反应、自发放反应和信噪比。我们发现,吗啡暴露组神经元的最大视觉反应和自发放反应都显著性增大,信噪比变差。这意味着前者从噪声的背景中提取和传递信息的能力比后者弱。
通过本次实验,我们发现慢性吗啡暴露组和生理盐水对照组的对比度反应功能存在显著性差异。我们的实验结果证明了慢性吗啡暴露会影响视觉通路神经元的一个重要反应属性——对比度编码特性,这为研究慢性吗啡暴露导致视觉系统神经元功能障碍及相关行为学改变提供了又一个重要证据,也有助于我们更好地理解吗啡对视觉感知能力损害的机制。
二.GABA能系统影响猫视皮层神经元速度特性
感知物体运动信息是视觉系统的重要功能,而外界物体的速度信息在指导知觉判断和行为过程中扮演着关键角色。对视觉系统而言,速度是由时空频率决定的。如果一个神经元的最优速度并不随着时空频率的变化而改变,这样的神经元则被认为是“速度调谐”(speed tuned)的；反之,如果神经元的最优速度随着空间频率的变化而变化,那么这样的神经元则认为具有“时空频率分离调谐’'(separable tuning)特征。研究空间频率和速度之间的关系对于深入了解运动调谐具有重要意义。目前,对于猫视皮层神经元的最优速度和空间频率的关系还没有研究报道。
GABA能系统在维持视觉功能中发挥了重要的作用。一系列的研究表明GABA及其受体激动剂能改善视皮层神经元受损的细胞功能,而对于GABA能系统是否会影响到皮层神经元的速度特性尚未见报道。
在本实验中,我们分别研究了猫的初级视皮层V1区和纹外皮层PMLS区神经元的最优速度和空间频率之间的关系,并采用细胞外微电泳实验来研究GABA和GABAA受体选择性拮抗剂Bicuculline这两种药物对视皮层神经元最优速度与空间频率关系的影响。研究发现,GABA导致初级视皮层V1区和PMLS区神经元最优速度对空间频率的依赖减弱,而Bicuculline则导致初级视皮层V1区和PMLS区神经元最优速度对空间频率的依赖增大。此外,我们还发现与PMLS区相比,V1区神经元最优速度对空间频率的依赖性更强。
通过这次实验,我们发现微电泳药物组和对照组的速度调谐指数(Q)存在明显差异,不同脑区神经元的速度调谐指数也存在差异。我们的实验结果证明了GABA能系统会影响神经元的速度特性,从而影响其运动编码。
1. Chronic morphine exposure affects contrast response functions of V1neurons in cats
Drug abuse is a serious social and medical problem in the world. Chronic exposure to opiates eventually leads to physiological and psychological dependence and causes severe damage to the nervous system. It has been indicated that the visual system is rich in opiate receptors. Morphological and electrophysiological studies reveal that chronic morphine administration leads to the prominently structural modification in the primary visual cortex. Many visual response properties of the neurons in LGN and V1, such as response modulation, orientation and direction selectivity and the visual response latency, are found to be significantly affected by chronic morphine exposure.
Coding of contrast plays an important role in the visual information processing. Psychophysical studies indicate that human motion perception is contrast-dependent, such as speed perception, orientation discrimination and figure-ground segregation. It has als.o been suggested that variation of stimulus contrast can influence the neuronal tuning for other parameters, like spatial frequency and speed. Up to now, few studies have focused on the effects of opiates on contrast response function of the neurons in the visual cortex
In the present study, we have studied and compared contrast response functions of neurons in primary visual cortex (V1) in chronic morphine-treated cats (MCs) and saline-treated cats (SCs)(control) using extracellular single-unit recording techniques. We found that C50(half-saturation contrast) of both groups were normally distributed and significant differences were seen between these two distributions. C50in MCs varied with a wider range (from0.10to0.77) than those in SCs (from0.07to0.32), More than half of the cells (51.3%,41of80) in MCs showed low contrast sensitivity (C50≥0.3) while only7.0%of the cells (4of57) in SCs exhibited similar response property. On the other hand, the percentage of the cells that were highly contrast sensitive (C50<0.1) is greater in SCs (8.8%,5of57) than in MCs (2.5%,2of80) These findings indicate a substantial decline in contrast sensitivity induced by chronic morphine exposure. We also analyzed the maximum visual responses (Rmax), baseline responses (M) and the signal-to-noise ratios (SNR) of all recorded neurons in MCs and SCs. We found that cells in MCs exhibited significantly higher maximum visual responses and baseline responses than those in SCs. Signal-to-noise ratios of neurons in MCs were much smaller than those in SCs.
Our results that significant changes exist in contrast response function between MCs and SCs provide the first evidence of the influence of chronic morphine exposure on neuronal contrast encoding, which is an important response property of the neurons in the visual pathway. These findings provide new neurobiology evidence that chronic morphine exposure induces functional degradation of vision system and could be helpful for better understanding of the mechanism by which chronic morphine treatment impairs many aspects of visual perception,
2. GABA affects the neural representation of speed in Cats
The perception of speed is important for vision and plays a key role in perceptual judgments and motion actions. The speed of a grating stimulus is given by its temporal frequency divided by its spatial frequency. If the preferred speed is the same at all spatial frequency, then the temporal frequency tuning must vary as a function of spatial frequency:we say that the neuron is "speed tuned". If the preferred temporal frequency does not vary as a function of spatial frequency, then the preferred speed must vary with spatial frequency:we say that the neuron has "separable tuning" for spatial and temporal frequency. So far the speed tuning properties of neurons in cats are largely unknown.
GABAnergic system is critical for maintaining normal visual function. A lot of studies have demonstrated that GABA and GABAa receptor agonist could improve impaired neuronal functions in visual cortex. However, it is still unknown whether GABAnergic system affects speed tuning of neurons in cats.
In the present study, we used extracellular single-unit recording techniques to study the effect of spatial frequency on the preferred speed of neurons in areas V1and PMLS of anesthetized cats. Furthermore, we also studied the effects of electrophoretic application of the inhibitory transmitter GABA and the GABAA antagonist bicuculline on speed tuning properties of V1and PMLS neurons. We found that the preferred speed of V1and PMLS neurons became less dependent on spatial frequency following GABA treatment. On the contrary, bicuculline resulted in increased dependence of preferred speed of V1and PMLS neurons on spatial frequency. In addition, we also found the speed tuning of PMLS neurons depended less on spatial frequency than that of V1neurons.
In conclusion, the results of this study show that the speed tuning properties of V1and PMLS neurons are different and GABAnergic system affects speed tuning of neurons in cats.The present study also has implications for understanding speed tuning properties of neurons and visual motion processing.
引文
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