Hua Tianmiao, Kao Chuanchao, Sun Qingyan, Li Xiangrui, Zhou Yifeng
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
Brain Res Bull. 2008 Jan 31;75(1):119-25. doi: 10.1016/j.brainresbull.2007.08.001. Epub 2007 Sep 4.
Electrophysiological studies indicate that a decline of GABAergic inhibition in the visual cortex may underlie age-related degradation of visual function [A.G. Leventhal, Y. Wang, M. Pu, Y. Zhou, Y. Ma, GABA and its agonists improved visual cortical function in senescent monkeys, Science 300 (2003) 812-815; M.T. Schmolesky, Y. Wang, M. Pu, A.G. Leventhal, Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys, Nat. Neurosci. 3 (2000) 384-390]. To date, there is little direct evidence to support this hypothesis. Using Nissl staining and immunohistochemical techniques, we quantitatively compared the density of total neurons (Nissl-stained neurons) and GABA-immunoreactive neurons as well as the proportion of GABA-immunoreactive neurons to total neurons in the primary visual cortex between 4 young adult (1-3 year old) cats and 4 old (12 year old) cats, which had been previously examined in a single-unit recording study [T. Hua, X. Li, L. He, Y. Zhou, Y. Wang, A.G. Leventhal, Functional degradation of visual cortical cells in old cats, Neurobiol. Aging 27 (2006) 155-162]. In that study, we found the function of V(1) (area 17) neurons in the old cats was significantly degraded relative to young adult cats. Our present results indicate that the density of total neurons in each cortical layer of V(1) exhibit no significant difference in the two age groups of cats. However, the density of GABA-immunoreactive neurons in old cats is significantly lower than in young adults. Further, the ratio of GABA-immunoreactive neurons to total neurons in each layer of V(1) in old cats is also significantly decreased when compared to young adult cats. These results provide direct morphological evidence of decreased GABAergic inhibition in the striate visual cortex of old animals, which accompany the functional degradation of visual cortical neurons.
电生理研究表明,视觉皮层中γ-氨基丁酸(GABA)能抑制作用的下降可能是与年龄相关的视觉功能退化的基础[A.G. 莱文索尔、王宇、蒲明、周宇、马宇,《GABA及其激动剂改善衰老猴子的视觉皮层功能》,《科学》300 (2003) 812 - 815;M.T. 施莫列斯基、王宇、蒲明、A.G. 莱文索尔,《衰老恒河猴视觉皮层细胞刺激选择性的退化》,《自然神经科学》3 (2000) 384 - 390]。迄今为止,几乎没有直接证据支持这一假说。我们使用尼氏染色和免疫组织化学技术,对4只年轻成年猫(1 - 3岁)和4只老年猫(12岁)初级视觉皮层中总神经元(尼氏染色神经元)和GABA免疫反应性神经元的密度,以及GABA免疫反应性神经元占总神经元的比例进行了定量比较,这些猫之前已在一项单单位记录研究中接受过检测[T. 华、李霞、何丽、周宇、王宇、A.G. 莱文索尔,《老年猫视觉皮层细胞的功能退化》,《神经生物学衰老》27 (2006) 155 - 162]。在该研究中,我们发现老年猫V(1)(17区)神经元的功能相对于年轻成年猫有显著退化。我们目前的结果表明,在这两个年龄组的猫中,V(1)各皮层层的总神经元密度没有显著差异。然而,老年猫中GABA免疫反应性神经元的密度显著低于年轻成年猫。此外,与年轻成年猫相比,老年猫V(1)各层中GABA免疫反应性神经元与总神经元的比例也显著降低。这些结果为老年动物纹状视觉皮层中GABA能抑制作用降低提供了直接的形态学证据,这种降低与视觉皮层神经元的功能退化相伴。