【作者】 杨赟；

【导师】 周逸峰；

【作者基本信息】 中国科学技术大学 ， 生物物理学， 2008， 博士

【摘要】 正常老化过程常常伴随着视觉功能的进行性退化。眼睛光学性质和视网膜形态学的改变并不足以解释这些功能性退化,不少方面可能决定于老化引起的视觉中枢的变化。深入研究老化引起的皮层功能性变化对了解非病理性老化过程的机制及探讨延缓老化的途径都有重要意义。本研究采用在体细胞外单位记录方法,从以下四个方面进一步比较了青年和老年猕猴视觉皮层细胞反应特性的差异:1.研究了88个老年猕猴MT神经元和107个青年猕猴MT神经元对运动随机点的速度调谐曲线。我们发现,与青年猴相比,老年猕猴MT区细胞速度选择性显著下降,速度调谐曲线的最优速度朝低速偏移,同时自发放电活动、视觉刺激诱发反应强度和反应变异性显著增加,细胞活动信噪比则出现显著下降。而且,老年猕猴神经元对速度信息的调制能力和识别能力也显著弱于青年猴。同时,我们也估算了青年组和老年组猕猴的速度辨别阈值,发现老年猕猴的速度识别阈值显著高于青年猕猴。这些结果可能为老化引起的运动感知功能障碍提供必要的生理学基础。2.研究了老化对猕猴初级视皮层(V1)和MT区神经元对比度反应曲线的影响。与青年猕猴相比,老年猕猴V1和MT的对比敏感度均显著下降,MT区细胞受老化的影响更大。特别地,MT细胞受老化的影响更甚于V1区有方向选择性的细胞。这说明MT区表现出的老年性退化并非完全由V1区的变化引起的,老化的影响并不局限于V1,可能在皮层视觉通路中逐渐积累。另外,老年猕猴MT区细胞的非线性特性也明显弱于青年猕猴。以上的结果表明了在老化过程中,Magnocellular和Parvocellular通路均严重受损。我们的结果和老年皮层抑制的退化理论是一致的,可能为一些老年性视觉功能障碍提供生理依据。3.研究了老化对猕猴MT细胞对比度适应的影响。我们发现,由适应引起的老年猕猴细胞的反应增益变化显著高于青年细胞,而对比度增益变化则显著低于青年细胞。这些功能上的退化可能来自前一级皮层的输入,也可能与老年猕猴MT神经元自身疲劳机制和过度的兴奋性有关。4.研究了老化对V1和MT区细胞反应变应性的影响,希望能进一步了解老化过程对神经元信息处理能力的损害。我们发现,老年猴V1和MT区细胞的反应变异性增大,反应信噪比减小。这些变化可能会对视觉系统功能产生重要的影响,同时也反映了老化过程影响神经系统功能的一些普遍机制。老年动物视觉皮层兴奋系统与抑制系统的失衡和突触结构的改变可能介导了V1和MT区细胞的反应变异性异常。结论:猕猴MT区神经元对视觉刺激的反应特性呈现明显的年龄相关性变化。结果显示1)MT区神经元对速度信息的调谐特性受老化影响;2)与V1一样,老年猕猴MT区神经元的对比敏感度较之青年猴显著下降,而且MT受老化影响更为严重,这说明老化的影响可能在皮层视觉通路中逐渐积累;3)老年猕猴MT神经元的对比度适应出现异常;4)V1和MT的反应变异性显著受老化影响。这些结果可能为老年性视觉功能下降提供了必要的神经机制。更多还原

【Abstract】 Human visual abilities decline during normal aging. Much of the decline cannot be attributed to the optical changes of the eye or changes in the retina, but and most likely reflect aged-related changes in visual cortical areas. To reveal the neural mechanism underlyng the visual function degradation during noral aging is of great practical importance to how to improve life quality for the old population and to slow down the aging process in humans.Using single-unit extracellular recording techniques, we compared the response properties of visual cortical cells in young and old monkeys. Our main findings are as follows:1. Aging affects the neural representation of speed in macaque area MTIn the present study, we used random-dot patterns to study the effects of aging on speed tuning curves in cortical area MT of macaque visual cortex. Our results provide evidence for a significant degradation of speed selectivity in MT. Cells in old animals preferred lower speeds than did those in young animals. Response modulation and discriminative capacity for speed in old monkeys were also significantly weaker than those in young ones. Concurrently, MT cells in old monkeys showed increased baseline responses, peak responses and response variability. These changes were accompanied by very low signal-to-noise ratios. We also found that speed discrimination thresholds in old animals were higher than in young ones. The foregoing neural changes may mediate the declines in visual motion perception that occur during senescence.2. Aging affects contrast response functions of MT neurons in rhesus monkeysIn the present study we studied the effects of aging on the coding of contrast in area V1 (primary visual cortex) and MT (middle temporal visual area) of the macaque monkey using single-neuron in vivo electrophysiology. Our results show that both MT and V1 neurons in old monkeys are less sensitive to contrast than those in young monkeys. Generally, contrast sensitivity is affected by aging more severely in MT cells than in V1 cells. Specifically, MT cells were affected more severely than motion direction selective V1 cells. Our results suggest that there may be an anomalous visual processing in both the magnocellular and parvocellular pathways. The neural changes described here are consistent with an age-related degeneration of intracortical inhibition and could underlie some deficits in visual function during normal aging.3. Aging affects contrast adaptation of MT neurons in rhesus monkeysWe assessed age-related changes of neuronal adaptation to visual motion in MT. We also found age-related changes in neuronal adaptation to visual motion in MT. Compared to young animals, the contrast gain of MT neurons in old monkeys are less affected, but the response gain by adaptation of MT neurons are more affected. This may reflect a ’fatigue’ mechanism and excitotoxic hyperactivity in old brains.4. Aging affects response variability of V1 and MT neurons in rhesus monkeysWe examined how aging affects response variability of V1 and MT in rhesus (Macaca mulatta) monkeys. We found that mean response and response variability in both V1 and MT of old monkeys are significantly higher than in young monkeys. And signal-to-noise ratio in old monkeys is significantly lower than in young ones. The results are consistent with an age-related degradation of inhibitory intracortical circuits. The neural changes described here could contribute to declines in visual function during senescence.In summary, age-related changes in macaque MT were observed in the present study. The results indicated 1) the neural representation of speed in macaque area MT is affected by aging; 2) there is more severe functional degradation of higher areas in visual hirerchy; 3) the age-related changes in neuronal adaptation to visual motion in MT occur; 4) spike count variability in V1 and MT of old monkeys is significantly higher than young monkeys. All of the findings provide us a more comprehensive understanding about the mechanisms underlying the age-related degeneration of visual function.更多还原