年龄及性别相关的大鼠视皮层细胞的功能衰退
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摘要
人和动物的视皮层功能会随着年龄的增长出现衰退，如老年视皮层双眼细胞减少；老年视皮层细胞对视觉刺激的方位及运动方向判别能力下降；对视觉信号的分析及提取速度显著下降，反应延迟明显增长；对视觉信号的提取能力显著下降，对图形的适应性增强，这些皮层功能的衰退可能是导致视觉功能年龄相关衰退的生理基础。目前的很多研究表明皮层功能衰退部分是由老年皮层抑制系统的退化所导致，老年皮层突触结构的丢失也是皮层功能衰退的潜在机制。深入探讨随年龄产生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衰老的途径的都十分有意义。
本研究采用在体场电位和细胞外单细胞记录方法，比较了老年和青年大鼠视皮层—外膝体通路的短时程突触可塑性，比较了老年和青年大鼠初级视皮层对闪光刺激的反应调制特性。此外，我们还比较了不同性别老年大鼠的视皮层功能衰退的可能差异。最后，我们用免疫组织化学的方法研究了神经递质GABA免疫神经元在老年和青年大鼠初级视皮层分布的差异。主要取得以下结果。
1．比较了5只老年大鼠和6只青年大鼠外膝体—皮层视觉通路的短时程突触可塑性的特点，发现老年大鼠在25ms-1000ms间隔的双脉冲刺激抑制比和10Hz～40Hz的串刺激抑制比都要显著的高于青年大鼠。该结果提示老年大鼠皮层内的抑制性降低，这可能与年龄相关的皮层内GABA能系统退化有关。
2．研究了青年大鼠初级视皮层51个神经元和老年大鼠初级视皮层46个神经元对1，2，4，8 Hz闪光刺激反应的特性。发现老年大鼠初级视皮层神经元的闪光刺激适应系数Ai(Ai定义为反应平台期的平均发放数比初始反应的平均发放数)的平均值在4Hz(young：0.42±0.02；aged：0.33±0.02，P＜0.01 t-test)和8Hz(young：0.32±0.02；aged：0.17+0.01；P＜0.0001 t-test)比青年大鼠要显著降低，表明老年大鼠V1区神经元对高频闪光刺激的适应明显强于青年大鼠。这一结果可能与老年大鼠皮层神经元更易疲劳有关。此外，对比于青年大鼠，老年大鼠初级视皮层神经元的自发放频率显著增高、信号—噪音比显著降低、对闪光刺激的反应潜伏期显著延长。我们的结果提示：老年大鼠初级视皮层神经元的多种反应特性都比青年大鼠显著的衰退。
Visual functions deteriorate gradually during normal aging process, such as the decrease of visual acuity and contrast sensitivity, impairment in the ability of orientation discrimination and motion direction as well as reduction of eyes summation and temporal processing speed. Age related visual function declines can not be attributed completely to changes in optical media and retinal morphology. Considerable visual functions impairment in the old may result from neuronal morphological changes or transmitter pathways degeneration (such as weakened GABA inhibition) in the visual processing centers, such as the primary visual cortex. To uncover the neural mechanism underlying the visual function degradation is of great practical importance to how to improve life quality for the old population and to slow down the aging process in human beings.
Using in vivo field potentials recording and extracellular single-unit recording techniques, we compared the short-term synaptic plasticity of geniculo-cortical visual pathway in aged and young rats. The response properties of primary visual cortical cells to flash stimuli in aged and young rats were also examined. Moreover, we investigated the sexual difference of visual cortex's function in aged rats. The density of GABA-immunoreactive neurons in primary visual cortex was quantitatively studied by immunohistochemistry method. Main results are as following:
1. We compared the short-term synaptic plasticity of geniculo-cortical visual pathway in five aged rats and six young rats. Our results showed either the pair-pulse depression ratio with interstumilus intervals from 25 ms to 1000ms or the frequency depression ratio at 10 Hz~40 Hz were significantly high in aged rats. The decreased short-term depression suggests the degradation of inhibition system in cortex of aged rats, which may be related to the degradation of GABAergic system during aging.
2. Response properties of primary visual cortical cells to 1, 2, 4, 8 Hz flash stimuli
本研究采用在体场电位和细胞外单细胞记录方法，比较了老年和青年大鼠视皮层—外膝体通路的短时程突触可塑性，比较了老年和青年大鼠初级视皮层对闪光刺激的反应调制特性。此外，我们还比较了不同性别老年大鼠的视皮层功能衰退的可能差异。最后，我们用免疫组织化学的方法研究了神经递质GABA免疫神经元在老年和青年大鼠初级视皮层分布的差异。主要取得以下结果。
1．比较了5只老年大鼠和6只青年大鼠外膝体—皮层视觉通路的短时程突触可塑性的特点，发现老年大鼠在25ms-1000ms间隔的双脉冲刺激抑制比和10Hz～40Hz的串刺激抑制比都要显著的高于青年大鼠。该结果提示老年大鼠皮层内的抑制性降低，这可能与年龄相关的皮层内GABA能系统退化有关。
2．研究了青年大鼠初级视皮层51个神经元和老年大鼠初级视皮层46个神经元对1，2，4，8 Hz闪光刺激反应的特性。发现老年大鼠初级视皮层神经元的闪光刺激适应系数Ai(Ai定义为反应平台期的平均发放数比初始反应的平均发放数)的平均值在4Hz(young：0.42±0.02；aged：0.33±0.02，P＜0.01 t-test)和8Hz(young：0.32±0.02；aged：0.17+0.01；P＜0.0001 t-test)比青年大鼠要显著降低，表明老年大鼠V1区神经元对高频闪光刺激的适应明显强于青年大鼠。这一结果可能与老年大鼠皮层神经元更易疲劳有关。此外，对比于青年大鼠，老年大鼠初级视皮层神经元的自发放频率显著增高、信号—噪音比显著降低、对闪光刺激的反应潜伏期显著延长。我们的结果提示：老年大鼠初级视皮层神经元的多种反应特性都比青年大鼠显著的衰退。
Visual functions deteriorate gradually during normal aging process, such as the decrease of visual acuity and contrast sensitivity, impairment in the ability of orientation discrimination and motion direction as well as reduction of eyes summation and temporal processing speed. Age related visual function declines can not be attributed completely to changes in optical media and retinal morphology. Considerable visual functions impairment in the old may result from neuronal morphological changes or transmitter pathways degeneration (such as weakened GABA inhibition) in the visual processing centers, such as the primary visual cortex. To uncover the neural mechanism underlying the visual function degradation is of great practical importance to how to improve life quality for the old population and to slow down the aging process in human beings.
Using in vivo field potentials recording and extracellular single-unit recording techniques, we compared the short-term synaptic plasticity of geniculo-cortical visual pathway in aged and young rats. The response properties of primary visual cortical cells to flash stimuli in aged and young rats were also examined. Moreover, we investigated the sexual difference of visual cortex's function in aged rats. The density of GABA-immunoreactive neurons in primary visual cortex was quantitatively studied by immunohistochemistry method. Main results are as following:
1. We compared the short-term synaptic plasticity of geniculo-cortical visual pathway in five aged rats and six young rats. Our results showed either the pair-pulse depression ratio with interstumilus intervals from 25 ms to 1000ms or the frequency depression ratio at 10 Hz~40 Hz were significantly high in aged rats. The decreased short-term depression suggests the degradation of inhibition system in cortex of aged rats, which may be related to the degradation of GABAergic system during aging.
2. Response properties of primary visual cortical cells to 1, 2, 4, 8 Hz flash stimuli
引文
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华田苗 老年猫视皮层细胞的功能衰退及形态学研究 中国科技大学博士论文 2004