Rebola Nelson, Lujan Rafael, Cunha Rodrigo A, Mulle Christophe
Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra 3004-504, Portugal.
Neuron. 2008 Jan 10;57(1):121-34. doi: 10.1016/j.neuron.2007.11.023.
The physiological conditions under which adenosine A2A receptors modulate synaptic transmission are presently unclear. We show that A2A receptors are localized postsynaptically at synapses between mossy fibers and CA3 pyramidal cells and are essential for a form of long-term potentiation (LTP) of NMDA-EPSCs induced by short bursts of mossy fiber stimulation. This LTP spares AMPA-EPSCs and is likely induced and expressed postsynaptically. It depends on a postsynaptic Ca2+ rise, on G protein activation, and on Src kinase. In addition to A2A receptors, LTP of NMDA-EPSCs requires the activation of NMDA and mGluR5 receptors as potential sources of Ca2+ increase. LTP of NMDA-EPSCs displays a lower threshold for induction as compared with the conventional presynaptic mossy fiber LTP; however, the two forms of LTP can combine with stronger induction protocols. Thus, postsynaptic A2A receptors may potentially affect information processing in CA3 neuronal networks and memory performance.
目前尚不清楚腺苷A2A受体调节突触传递的生理条件。我们发现,A2A受体位于苔藓纤维与CA3锥体细胞之间突触的突触后部位,对于由苔藓纤维短串刺激诱导的NMDA-EPSCs的一种长时程增强(LTP)形式至关重要。这种LTP不影响AMPA-EPSCs,并且可能在突触后诱导和表达。它依赖于突触后Ca2+升高、G蛋白激活和Src激酶。除A2A受体外,NMDA-EPSCs的LTP还需要激活NMDA和mGluR5受体作为Ca2+增加的潜在来源。与传统的突触前苔藓纤维LTP相比,NMDA-EPSCs的LTP诱导阈值更低;然而,这两种LTP形式可以通过更强的诱导方案结合起来。因此,突触后A2A受体可能会潜在地影响CA3神经元网络中的信息处理和记忆表现。