Salinska E J, Chaudhury D, Bourne R C, Rose S P
Department of Neurochemistry, Medical Research Centre, Warsaw, Poland.
Neuroscience. 1999;93(4):1507-14. doi: 10.1016/s0306-4522(99)00281-x.
A temporal cascade of events has been described from a number of biochemical investigations of passive avoidance training in day-old chicks. Among these, within minutes of training, there is a transient, enhanced release of glutamate and increased agonist and antagonist binding to N-methyl-D-aspartate-sensitive glutamate receptors in the intermediate medial hyperstriatum ventrale of the forebrain. Some 6.5 h later, alpha-amino-3-hydroxy-5-methyl-4-isoxazo lepropionate binding to glutamate receptors is also increased in the same region. These processes might be predicted to affect the uptake of calcium via voltage-sensitive calcium channels or glutamate receptor-associated channels, thereby changing the intracellular calcium concentration. To test this possibility, we have measured the calcium concentration in synaptoneurosomes, containing both pre- and postsynaptic elements, prepared from left and right intermediate medial hyperstriatum ventrale at various times following training, using Fura 2-AM as the indicator of intracellular calcium concentration. Synaptoneurosomes, prepared immediately and 5 min after training, were stimulated with 70 mM potassium chloride in the presence of 2 mM calcium, resulting in a significantly enhanced increase in calcium concentration in synaptoneurosomes from the left hemisphere of trained chicks. This effect was absent in samples obtained at later times after training. N-Methyl-D-aspartate (0.5 mM) induced a significant enhancement in the increase in calcium concentration in intermediate medial hyperstriatum ventrale from both left and right hemispheres 10 min and 30 min after training. At 3 h and 6 h after training, alpha-amino-3-hydroxy-5-methyl-4-isoxazo lepropionate (0.5 mM) induced a significantly enhanced increase in calcium concentration in samples from either hemisphere. These results suggest that immediately after training there is an engagement of both pre- and postsynaptic voltage-sensitive calcium channels, followed by an increased reponse to N-methyl-D-aspartate receptor stimulation, and coinciding with the enhanced calcium-dependent glutamate release and an increase in N-methyl-D-aspartate-sensitive glutamate receptor binding that has been reported previously. The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-sensitive mechanisms are activated at a later stage of memory formation, when increased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding to glutamate receptors has been reported. Thus, responsiveness of calcium channels to agonist stimulation is implicated in temporally diverse stages in the cascade of events involved in memory formation following passive avoidance training in the chick.
通过对一日龄雏鸡被动回避训练的多项生化研究，已描述了一系列时间上的事件。其中，训练后数分钟内，前脑中间内侧腹侧纹状体中谷氨酸会短暂增强释放，且激动剂和拮抗剂与N-甲基-D-天冬氨酸敏感型谷氨酸受体的结合增加。约6.5小时后，同一区域中与谷氨酸受体结合的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸也会增加。这些过程可能会影响通过电压敏感型钙通道或谷氨酸受体相关通道的钙摄取，从而改变细胞内钙浓度。为了验证这种可能性，我们使用Fura 2-AM作为细胞内钙浓度的指示剂，测量了在训练后不同时间从左右中间内侧腹侧纹状体制备的、包含突触前和突触后成分的突触神经小体中的钙浓度。训练后立即和5分钟制备的突触神经小体，在存在2 mM钙的情况下用70 mM氯化钾刺激，导致训练雏鸡左半球突触神经小体中的钙浓度显著增强增加。训练后较晚时间获得的样本中没有这种效应。训练后10分钟和30分钟，N-甲基-D-天冬氨酸（0.5 mM）诱导左右半球中间内侧腹侧纹状体中钙浓度增加显著增强。训练后3小时和6小时，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（0.5 mM）诱导任一半球样本中钙浓度增加显著增强。这些结果表明，训练后立即突触前和突触后电压敏感型钙通道均被激活，随后对N-甲基-D-天冬氨酸受体刺激的反应增加，这与先前报道的钙依赖性谷氨酸释放增强和N-甲基-D-天冬氨酸敏感型谷氨酸受体结合增加相吻合。当已报道与谷氨酸受体结合的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸增加时，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸敏感机制在记忆形成的后期被激活。因此，钙通道对激动剂刺激的反应性与雏鸡被动回避训练后记忆形成所涉及的一系列事件中不同时间阶段有关。
