Activation of adenosine A2A receptor facilitates brain-derived neurotrophic factor modulation of synaptic transmission in hippocampal slices

被引:143
作者
Diógenes, MJ
Fernandes, CC
Sebastiao, AM
Ribeiro, JA
机构
[1] Univ Lisbon, Fac Med, Neurosci Lab, P-1649028 Lisbon, Portugal
[2] Univ Lisbon, Fac Med, Inst Pharmacol, Inst Mol Med, P-1649028 Lisbon, Portugal
关键词
adenosine receptors; BDNF; hippocampus; synaptic transmission; neuromodulation; neurotrophic factors;
D O I
10.1523/JNEUROSCI.4454-03.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Both brain-derived neurotrophic factor (BDNF) and adenosine influence neuronal plasticity. We now investigated how adenosine influences the action of BDNF on synaptic transmission in the CA1 area of the rat hippocampal slices. Alone, BDNF (20-100 ng/ml) did not significantly affect field EPSPs (fEPSPs). However, a 2 min pulse of high-K+ (10 mM) 46 min before the application of BDNF (20 ng/ml) triggered an excitatory action, an effect blocked by the TrkB receptor inhibitor K252a (200 nM), by the adenosine A(2A) receptor antagonist ZM241385 (50 nM), and by the protein kinase A inhibitor H-89 (1 muM). Presynaptic, rather than postsynaptic depolarization was required to trigger the BDNF action because after K+ depolarization BDNF also increased EPSCs recorded from pyramidal neurons voltage-clamped at -60 mV, and transient postsynaptic depolarization was unable to unmask the BDNF action. A weak theta burst stimulation of the afferents could elicit potentiation of synaptic transmission only when applied in the presence of BDNF. Activation of adenosine A(2A) receptors with CGS 21680 (10 nM), or the increase in extracellular adenosine levels induced by 5-iodotubercidin (100 nM) triggered the excitatory action of BDNF, a process prevented by ZM241385 and by H-89. In the presence of dibutyryl-cAMP (0.5 mM), BDNF also increased fEPSPs but postsynaptic cAMP (0.5 mM) was unable to trigger the BDNF action. It is concluded that presynaptic activity-dependent release of adenosine, through activation of A(2A) receptors, facilitates BDNF modulation of synaptic transmission at hippocampal synapses.
引用
收藏
页码:2905 / 2913
页数:9
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