Gurden H, Takita M, Jay T M
Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8620, 91405 Orsay, France.
J Neurosci. 2000 Nov 15;20(22):RC106. doi: 10.1523/JNEUROSCI.20-22-j0003.2000.
An intact mesocortical dopaminergic (DA) input to the prefrontal cortex (PFC) has been reported to be necessary for long-term potentiation (LTP) to occur at hippocampal-prefrontal cortex synapses. Here, we investigated the role of D1 and D2 receptors in this NMDA receptor-dependent LTP. Local infusion of the D1 agonist SKF81297 at an optimal dose induced a sustained enhancement of hippocampal-PFC LTP, whereas the D1 antagonist SCH23390 caused a dose-related impairment of its induction. The D1 agonist effect was mimicked by infusion of a low dose of the adenylyl cyclase activator forskolin, whereas LTP was severely attenuated with a protein kinase A inhibitor, Rp-cAMPS. To further assess the complex interplay between DA and NMDA receptors, changes in extracellular DA levels in the PFC were estimated during LTP, and a significant increase was observed immediately after tetanus. Taken together, these data suggest that D1 but not D2 receptors are crucial for the DA control of the NMDA receptor-mediated synaptic response on a specific excitatory input to the PFC. The interactions of these receptors may play a crucial role in the storage and transfer of hippocampal information in the PFC.
据报道，前额叶皮质（PFC）完整的中脑皮质多巴胺能（DA）输入对于海马-前额叶皮质突触处发生长时程增强（LTP）是必要的。在此，我们研究了D1和D2受体在这种依赖N-甲基-D-天冬氨酸（NMDA）受体的LTP中的作用。以最佳剂量局部注入D1激动剂SKF81297可诱导海马-前额叶皮质LTP的持续增强，而D1拮抗剂SCH23390则导致其诱导出现剂量相关的损伤。注入低剂量的腺苷酸环化酶激活剂福斯高林可模拟D1激动剂的作用，而蛋白激酶A抑制剂Rp-cAMPS则会严重减弱LTP。为了进一步评估DA和NMDA受体之间的复杂相互作用，在LTP期间估计了PFC中细胞外DA水平的变化，并且在强直刺激后立即观察到显著增加。综上所述，这些数据表明D1而非D2受体对于DA控制PFC特定兴奋性输入上的NMDA受体介导的突触反应至关重要。这些受体之间的相互作用可能在海马信息在PFC中的存储和传递中起关键作用。
