Giovannini Maria Grazia, Efoudebe Marcel, Passani Maria Beatrice, Baldi Elisabetta, Bucherelli Corrado, Giachi Filippo, Corradetti Renato, Blandina Patrizio
Dipartimento di Farmacologia Preclinica e Clinica, Universitá di Firenze, 50139 Firenze, Italy.
J Neurosci. 2003 Oct 8;23(27):9016-23. doi: 10.1523/JNEUROSCI.23-27-09016.2003.
Consolidation of associative memories appears to require extracellular signal-related kinase2 (ERK2) activation, which is modulated by several factors, including neurotransmitter receptor stimulation. Here we show that in vitro stimulation of either H2 or H3 histaminergic receptors activates ERK2 in hippocampal CA3 pyramidal cells. In behaving animals, bilateral posttraining injections into the dorsal hippocampus of histamine H2 or H3 receptor agonists improve memory consolidation after contextual fear conditioning. Local administration of U0126, a selective inhibitor of ERK kinase, prevents memory improvements exerted by the agonists, without causing any behavioral effect per se. This is the first evidence of a positive correlation between ERK phosphorylation and memory improvement. Moreover, we demonstrate that the brain histaminergic system regulates hippocampal ERK cascade. Finally, our data indicate that early ERK2 hippocampal activation is not required for the expression of long-term fear memories.
关联性记忆的巩固似乎需要细胞外信号调节激酶2（ERK2）的激活，而ERK2的激活受多种因素调控，包括神经递质受体刺激。在此我们表明，体外刺激H2或H3组胺能受体会激活海马CA3锥体细胞中的ERK2。在行为动物中，组胺H2或H3受体激动剂在训练后双侧注射到背侧海马中可改善情境恐惧条件反射后的记忆巩固。ERK激酶的选择性抑制剂U0126的局部给药可阻止激动剂所带来的记忆改善，且本身不会引起任何行为效应。这是ERK磷酸化与记忆改善之间存在正相关的首个证据。此外，我们证明大脑组胺能系统调节海马ERK级联反应。最后，我们的数据表明长期恐惧记忆的表达并不需要早期海马ERK2的激活。
