Rosenblum K, Schul R, Meiri N, Hadari Y R, Zick Y, Dudai Y
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1157-61. doi: 10.1073/pnas.92.4.1157.
Protein tyrosine phosphorylation is a major signal transduction pathway involved in cellular metabolism, growth, and differentiation. Recent data indicate that tyrosine phosphorylation also plays a role in neuronal plasticity. We are using conditioned taste aversion, a fast and robust associative learning paradigm subserved among other brain areas by the insular cortex, to investigate molecular correlates of learning and memory in the rat cortex. In conditioned taste aversion, rats learn to associate a novel taste (e.g., saccharin) with delayed poisoning (e.g., by LiCl injection). Here we report that after conditioned taste aversion training, there is a rapid and marked increase in tyrosine phosphorylation of a set of proteins in the insular cortex but not in other brain areas. A major protein so modulated, of 180 kDa, is abundant in a membrane fraction and remains modulated for more than an hour after training. Exposure of the rats to the novel taste alone results in only a small modulation of the aforementioned proteins whereas administration of the malaise-inducing agent per se has no effect. To the best of our knowledge, this is the first demonstration of modulation of protein tyrosine phosphorylation in the brain after a behavioral experience.
蛋白质酪氨酸磷酸化是参与细胞代谢、生长和分化的主要信号转导途径。最近的数据表明，酪氨酸磷酸化在神经元可塑性中也发挥作用。我们正在利用条件性味觉厌恶，一种快速且强大的联想学习范式，该范式在其他脑区中由岛叶皮层支持，来研究大鼠皮层中学习和记忆的分子关联。在条件性味觉厌恶中，大鼠学会将一种新口味（如糖精）与延迟中毒（如通过注射氯化锂）联系起来。在此我们报告，在条件性味觉厌恶训练后，岛叶皮层中一组蛋白质的酪氨酸磷酸化迅速且显著增加，而其他脑区则没有。一种主要的受调节蛋白质，分子量为180 kDa，在膜组分中含量丰富，训练后可保持调节状态超过一小时。仅让大鼠接触新口味只会对上述蛋白质产生轻微调节，而单独给予引起不适的药剂则没有效果。据我们所知，这是行为经历后大脑中蛋白质酪氨酸磷酸化调节的首次证明。
