Navakkode Sheeja, Sajikumar Sreedharan, Frey Julietta Uta
Leibniz Institute for Neurobiology, Department of Neurophysiology, Magdeburg, Germany.
Neuropharmacology. 2007 Jun;52(7):1547-54. doi: 10.1016/j.neuropharm.2007.02.010. Epub 2007 Mar 12.
Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory and its cellular model, i.e. hippocampal long-term potentiation (LTP) in CA1. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (late-LTP) by activating the cAMP/PKA-pathway. In earlier studies we had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D-aspartate (NMDA)-receptors (Frey, 2001, Long-lasting hippocampal plasticity: cellular model for memory consolidation? In: Richter, D. (Ed.), Cell Polarity and Subcellular RNA Localization. Springer-Verlag, Berlin-Heidelberg, pp. 27-40). Interestingly, the short-term application of D1/D5-receptor agonists (SKF38393 or 6-bromo-APB, 50 microM) can induce a slow-onset potentiation. This D1/D5-agonist-induced delayed-onset potentiation (D1/D5-LTP) resembles late-LTP, i.e. it is dependent on protein synthesis in the CA1 of rat hippocampal slices in vitro. The question arises as to whether D1/D5-LTP also requires glutamatergic stimulation, i.e. NMDA-receptor activation. We provide first evidence that a synergistic role of D1/D5- as well as NMDA-receptor-function is required in mediating processes relevant for the maintenance of this protein synthesis-dependent potentiation.
多巴胺能D1/D5受体介导的过程对于某些形式的记忆及其细胞模型（即CA1区的海马长时程增强效应，LTP）而言至关重要。通过激活cAMP/PKA信号通路，D1/D5受体功能是诱导CA1-LTP（晚期LTP）的蛋白质合成依赖性维持所必需的。在早期研究中，我们报道了D1/D5受体功能与N-甲基-D-天冬氨酸（NMDA）受体之间的协同相互作用（Frey，2001年，《持久的海马可塑性：记忆巩固的细胞模型？》，载于：Richter，D.（编），《细胞极性与亚细胞RNA定位》。施普林格出版社，柏林-海德堡，第27 - 40页）。有趣的是，短期应用D1/D5受体激动剂（SKF38393或6-溴-APB，50微摩尔）可诱导缓慢起效的增强效应。这种D1/D5激动剂诱导的延迟起效增强效应（D1/D5-LTP）类似于晚期LTP，即它在体外大鼠海马切片的CA1区依赖于蛋白质合成。问题在于D1/D5-LTP是否也需要谷氨酸能刺激，即NMDA受体激活。我们提供了首个证据，表明在介导与这种蛋白质合成依赖性增强效应维持相关的过程中，D1/D5以及NMDA受体功能具有协同作用。
