Szapiro G, Izquierdo L A, Alonso M, Barros D, Paratcha G, Ardenghi P, Pereira P, Medina J H, Izquierdo I
Instituto de Biologia Celular y Neurociencias Eduardo de Robertis:, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 3er. Piso, (1121), Buenos Aires, Argentina.
Neuroscience. 2000;99(1):1-5. doi: 10.1016/s0306-4522(00)00236-0.
The ability to recall past events is a major determinant of survival strategies in all species and is of paramount importance in determining our uniqueness as individuals. In contrast to memory formation, the information about the molecular mechanisms of memory retrieval is surprisingly scarce and fragmentary. Here we show that pretest inhibition of the specific upstream activator of mitogen-activated protein kinase kinase, or of protein kinase A in the hippocampus, blocked retrieval of long-term memory for an inhibitory avoidance task, a hippocampal-dependent learning task. An activator of protein kinase A enhanced retrieval. Mitogen-activated protein kinase activation increased in the hippocampus during retrieval, while protein kinase A activity remained unchanged. Pretest intrahippocampal blockade of metabotropic glutamate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazolone propionic acid/kainate receptors, but not N-methyl-D-aspartate receptors or calcium/calmodulin dependent-protein kinase II, impaired retrieval. Thus, recall of inhibitory avoidance activates mitogen-activated protein kinase, which is necessary, along with metabotropic glutamate receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolone propionic acid/kainate receptors, and protein kinase A, for long-term memory expression. Our results indicate that memory formation and retrieval may share some molecular mechanisms in the hippocampus.
回忆过去事件的能力是所有物种生存策略的主要决定因素，对于确定我们作为个体的独特性至关重要。与记忆形成相比，关于记忆检索分子机制的信息出奇地稀少且支离破碎。在此我们表明，在海马体中对丝裂原活化蛋白激酶激酶的特定上游激活剂或蛋白激酶A进行预测试抑制，会阻断对抑制性回避任务（一种依赖海马体的学习任务）的长期记忆检索。蛋白激酶A的激活剂可增强检索。在检索过程中，海马体中的丝裂原活化蛋白激酶激活增加，而蛋白激酶A的活性保持不变。预测试海马体内代谢型谷氨酸受体或α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/海人藻酸受体的阻断，但不是N-甲基-D-天冬氨酸受体或钙/钙调蛋白依赖性蛋白激酶II的阻断，会损害检索。因此，抑制性回避的回忆会激活丝裂原活化蛋白激酶，这与代谢型谷氨酸受体、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/海人藻酸受体以及蛋白激酶A一起，对于长期记忆表达是必需的。我们的结果表明，记忆形成和检索可能在海马体中共享一些分子机制。
