Department of General Zoology and Neurobiology, Ruhr-University Bochum, ND 7/31, 44780 Bochum, Germany.
Exp Brain Res. 2009 Dec;199(3-4):345-53. doi: 10.1007/s00221-009-1722-8.
Albinism affects the anatomy and physiology of the visual system in mammals. Behavioural, anatomical and in vivo electrophysiological investigations revealed that the optokinetic reflex is abnormal and retinal slip neurons in the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system (NOT-DTN) lack direction selectivity and have a reduced dendritic tree in albinotic rats and ferrets. Earlier investigations show a disturbed chloride homeostasis and a depolarizing action of GABAergic currents in visual cortex cells of albinotic rats. We assume that an altered local inhibition could be one critical factor explaining the loss of direction selectivity in DTN neurons. To test this patch clamp analysis of NO-TDTN neurons in 250 μm thick acute brain slices from pigmented and albinotic rats were performed. GABAergic IPSCs were elicited by lateral current stimulation and the reversal potentials of GABA(A-) mediated currents (E(GABA)) were determined. Our results show a significantly more negative E(GABA) in NOT-DTN neurons of pigmented (-62.1 mV, ±10.8 mV, n=24) than of albinotic rats (-49.2 mV, ±17.7 mV, n=19; P<0.001). Control measurements in the superficial layer of the superior colliculus revealed no significant differences between pigmented (-56.2 mV, ±16.4 mV, n=17) and albinotic rats (-60.7 mV, ±13.8 mV, n=28; P>0.324). A similar shift in reversal potential of GABA(A-)mediated currents was observed also in pyramidal cells in layers II/III and V of the visual cortex and was explained by an accumulation of intracellular chloride due to an abnormal activity of chloride co-transporters. As described for retinal ganglion cells and cortical neurons, direction selectivity is formed by a balanced excitatory and inhibitory input. Our combined data suggest that the observed shift in reversal potential and a possible dysfunction of inhibitory interneurons might indeed be one factor responsible for the reduction of direction selectivity in the NOT-DTN and therefore for the pathology of the optokinetic response in albino mammals.
白化病会影响哺乳动物视觉系统的解剖结构和生理学。行为学、解剖学和活体电生理学研究表明，视动反射异常，并且在白化大鼠和雪貂的视束核和副视束系统背终核（NOT-DTN）中的视网膜滑神经元缺乏方向选择性，并且树突分支减少。早期的研究表明，白化大鼠视皮层细胞中氯离子稳态失调和 GABA 能电流去极化。我们假设，局部抑制的改变可能是解释 DTN 神经元方向选择性丧失的一个关键因素。为了验证这一点，我们在来自色素正常和白化大鼠的 250μm 厚急性脑切片上进行了 NO-TDTN 神经元的膜片钳分析。通过侧向电流刺激诱发 GABA 能 IPSCs，并确定 GABA(A-)介导电流的反转电位（E(GABA)）。我们的结果显示，在 NOT-DTN 神经元中，色素正常大鼠的 E(GABA)明显更负（-62.1 mV，±10.8 mV，n=24），而白化大鼠的 E(GABA)更负（-49.2 mV，±17.7 mV，n=19；P<0.001）。在浅层上丘进行的对照测量显示，色素正常大鼠（-56.2 mV，±16.4 mV，n=17）和白化大鼠（-60.7 mV，±13.8 mV，n=28；P>0.324）之间没有显著差异。在视觉皮层的 II/III 和 V 层中的锥体神经元中也观察到 GABA(A-)介导电流的反转电位类似的偏移，这是由于氯离子共转运体的异常活性导致细胞内氯离子积累所致。正如描述的视网膜神经节细胞和皮层神经元一样，方向选择性是由平衡的兴奋性和抑制性输入形成的。我们的综合数据表明，观察到的反转电位偏移和抑制性中间神经元的可能功能障碍确实可能是导致 NOT-DTN 方向选择性降低以及白化哺乳动物视动反应病理学的一个因素。
