Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine

Activation of Adenosine A2A Receptors Induces TrkB Translocation and Increases BDNF-Mediated Phospho-TrkB Localization in Lipid Rafts: Implications for Neuromodulation

“…BDNF activates the TrkB tyrosine kinase receptor and the p75 receptor, which belongs to the tumor necrosis factor receptor family. We and others have reported that TrkB receptor function is modulated by activation of adenosine A 2A receptors (Lee and Chao, 2001;Dió genes et al, 2004;Mojsilovic-Petrovic et al, 2006;Fontinha et al, 2008;Tebano et al, 2008). This TrkB/A 2A receptor cross talk has two consequences, which may operate independently: (1) facilitation of BDNF-induced actions on synaptic transmission and plasticity by A 2A receptor agonists; and (2) direct phosphorylation and activation of TrkB receptors, in the absence of BDNF, a process called transactivation.…”

Adenosine A2A Receptor Modulation of Hippocampal CA3-CA1 Synapse Plasticity During Associative Learning in Behaving Mice

“…In this regard, it has been shown recently that TrkB receptors located in the hippocampal circuit are involved in associative learning and in learning-induced changes in synaptic strength (Gruart et al, 2007). Adenosine A 2A receptors seem to be required for normal BDNF levels (Tebano et al, 2008), for BDNF-induced potentiation of synaptic transmission (Diógenes et al, 2007;Tebano et al, 2008), for BDNF influence upon alpha7-nicotinic acetylcholine receptors (Fernandes et al, 2008), andFmost relevant in the context of the present workFfor BDNF-induced facilitation of LTP (Fontinha et al, 2008) in the CA1 area of hippocampal slices. Indeed, upon blockade of A 2A receptors, BDNF was no longer able to facilitate theta-burst-induced CA1 LTP in hippocampal slices (Fontinha et al, 2008).…”

“…Adenosine A 2A receptors seem to be required for normal BDNF levels (Tebano et al, 2008), for BDNF-induced potentiation of synaptic transmission (Diógenes et al, 2007;Tebano et al, 2008), for BDNF influence upon alpha7-nicotinic acetylcholine receptors (Fernandes et al, 2008), andFmost relevant in the context of the present workFfor BDNF-induced facilitation of LTP (Fontinha et al, 2008) in the CA1 area of hippocampal slices. Indeed, upon blockade of A 2A receptors, BDNF was no longer able to facilitate theta-burst-induced CA1 LTP in hippocampal slices (Fontinha et al, 2008). Therefore, it is probable that a reduced influence of BDNF upon synaptic plasticity phenomena, due to the lack of activation of A 2A receptors by endogenous adenosine, might explain the now-reported associative learning disability of the animals with A 2A receptors blocked.…”

Adenosine A2A receptor activation is determinant for BDNF actions upon GABA and glutamate release from rat hippocampal synaptosomes

“…The different actions of A 2A Rs in different synapses and their ability to affect different actions of BDNF at specific sites of the tripartite synapse may allow to finely shape excitatory and inhibitory signals, thus to fine tune neuronal function. This probably has a greater impact upon synaptic plasticity rather than upon neuroprotection since BDNF actions on plasticity are known to be controlled by A 2A R [7,13,14], whereas neuroprotective actions of BDNF may not be affected by A 2A Rs [26].…”

“…Accordingly, there is evidence that activation of A 2A R induces the transactivation of TrkB-FL receptors [5,6], TrkB-FL translocation to lipid rafts [7], and regulates BDNF [8] and TrkB-FL levels [9]. Regarding functional evidence, it is clear that the facilitatory actions of BDNF upon CA1 hippocampal synaptic transmission [8,[10][11][12] and synaptic plasticity, both long-term potentiation [9,13,14] and long-term depression [15], are dependent on A 2A R activation. CA1 hippocampal synaptic activity relies, in part, on the dynamics of the most relevant neurotransmitters in this brain region, glutamate and GABA.…”