NMDA-Independent LTP by adenosine A2 receptor-mediated postsynaptic AMPA potentiation in hippocampus (original) (raw)
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NMDA-Independent LTP by Adenosine A2 Receptor-Mediated Postsynaptic AMPA Potentiation in Hippocampus
Journal of Neurophysiology, 1997
The role Adenosine has been shown to have a potent inhibitory effect of adenosine A 2 receptors in normal synaptic transmission and on neurotransmission in the hippocampus through activation tetanus-induced long-term potentiation (LTP) was tested by stimuof adenosine A 1 receptors (Dunwiddie et al. 1981; Greene lation of the Schaffer collateral pathway and recording of the field and Haas 1985), resulting in a decrease in transmitter release excitatory postsynaptic potential (EPSP) in the CA1 region of rat as well as modulation of transmembrane potassium and caltransverse hippocampal slices. Activation of adenosine A 2 recepcium currents. In addition to its inhibitory effect, adenosine tors with the A 2 agonist N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA; 20 nM) enhanced synaptic also has been shown to have an excitatory influence on syntransmission during low-frequency test pulses (0.033 Hz). Paired aptic transmission via activation of adenosine A 2 receptors stimulation before and during DPMA exposure indicated no paired-(Nishimura et al. 1990; Okada et al. 1992; Sebastiao and pulse facilitation as a result of A 2 activation, suggesting that en-Ribeiro 1996). hancement was not a result of presynaptic modulation. DPMA The A 1 and A 2 adenosine receptors were first differentiated enhanced the early phase a-amino-3-hydroxy-5-methyl-4-isoxabased on their ability to down-or upregulate adenylyl cyzolepropionic acid (AMPA) component of the EPSP. In contrast, clase (Londos and Wolff 1977; VanCalker et al. 1979), DPMA had no effect on the N-methyl-D-aspartate (NMDA) comrespectively. The A 2 receptor has been subdivided further ponent isolated using low extracellular Mg 2/ and the AMPA recepinto an A 2a and A 2b adenosine receptor (Bruns et al. 1986; tor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (20 mM), indicating that the effects of A 2 activation on synaptic transmission Ukena et al. 1986) based on its affinity for 5-N-ethylcarboxwere mediated by a postsynaptic enhancement of the AMPA reamidoadenosine with the A 2a receptor having the higher afsponse. Activation of adenosine A 2 receptors during a brief tetanus finity. Activation of A 2 receptors during tetanic stimulation (100 Hz, 1 s) increased the level of LTP by 36% over that seen has been shown to modulate the level of LTP achieved in a in response to a tetanus under control conditions. DPMA exposure adenosine 3,5-cyclic monophosphate (cAMP)-dependent after prior induction of LTP showed no additional potentiation,
Adenosine A2 receptors modulate hippocampal synaptic transmission via a cyclic-AMP-dependent pathway
Neuroscience, 1998
Blockade of adenosine A 2 receptors has been shown to significantly reduce the level of tetanus-induced long-term potentiation in area CA1 of rat hippocampus [Kessey K. et al. (1997) Brain Res. 756, 184-190;) Biochem. biophys. Res. Commun. 181, 1010-1014. In the present study, the effects of A 2 receptor activation and blockade on the modulation of normal synaptic transmission and tetanus-induced long-term potentiation were examined at the Schaffer-CA1 synapse in rat hippocampal slices. A 2 receptor activation reversibly enhanced synaptic transmission evoked by low-frequency test pulses as measured by the dendritic field excitatory postsynaptic potential. In the presence of A 1 receptor blockade, A 2 activation further enhanced the excitatory postsynaptic potential, while A 2 receptor blockade resulted in a reversible decrease of the excitatory postsynaptic potential. The A 2a receptor agonist, CGS21680, had no effect on the excitatory postsynaptic potential, suggesting that tonic activation of A 2b receptors contributes to synaptic transmission under normal physiological conditions. Furthermore, we investigated the contribution of A 2 receptors to the level of tetanus-induced long-term potentiation. Under control conditions, a single tetanus potentiated the excitatory postsynaptic potential by 63.5% relative to baseline 30 min post-tetanus. In contrast, tetanus-induced long-term potentiation during A 2 blockade was 21.3%. A 2 receptor activation increased the level of tetanus-induced long-term potentiation to 90.2%. Because A 2 receptors are known to stimulate cyclic-AMP accumulation, the possible involvement of cyclic-AMP was examined. Forskolin, a direct adenylate cyclase activator, and 8-bromo-cyclic-AMP, a membrane-permeable analog of cyclic-AMP, were able to reconstitute tetanusinduced long-term potentiation during A 2 receptor blockade; however, the inactive analog 1,9-dideoxyforskolin had no effect, indicating that the effects of A 2 activation on synaptic transmission were mediated largely through the regulation of intracellular cyclic-AMP.
Biochemical and Biophysical Research Communications, 1991
The effects of adenosine A2 receptor antagonist (CP-66713) on long-term potentiation were studied using guinea pig hippocampal slices in a perfusion system. Tetanic stimulation of Schaffer collateral input which was applied during perfusion of CP-66713 (10 PM), did not induce long-term potentiation but rather long-term depression of evoked synaptic potentials (field EPSP), but induced long-term potentiation of the population spike in CA1 neurons. Thus, adenosine derivatives which accumulate in the synaptic cleft during the tetanic stimulation may be involved in induction of the long term potentiation via A2 receptors at the synapse. The clear discrimination between long-term depression of the field EPSP and long-term potentiation of the population spike suggests EPSP-spike potentiation at the postsynaptic sites. o 1991 Academrc pre5s, Inc.
A role for adenosine A receptors in the induction of long-term potentiation
1997
Although reductions in neurotransmission have been reported in response to agonist-mediated adenosine A receptor activation, the 1 implications of A receptor activation on synaptic transmission have not been well explored. We examined the role adenosine A 2 2 receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A receptor blockade in the presence of complete A receptor inhibition led to a reversible reduction of the field excitatory post-synaptic 2 1 Ž . Ž . potential EPSP slope in response to low-frequency test pulses 0.033 Hz indicating that A receptors can enhance synaptic 2 Ž . transmission. A receptor blockade by the A antagonist, DMPX 3,7-dimethyl-1-propargylxanthine prevented the induction of 2 2 Ž . tetanus-induced long-term potentiation LTP of the EPSP. In contrast, no such effect on LTP induction was observed during A receptor 1 blockade. We also examined the effects of DMPX on the inductio...
Biomolecules
Adenosine operates a modulation system fine-tuning the efficiency of synaptic transmission and plasticity through A1 and A2A receptors (A1R, A2AR), respectively. Supramaximal activation of A1R can block hippocampal synaptic transmission, and the tonic engagement of A1R-mediated inhibition is increased with increased frequency of nerve stimulation. This is compatible with an activity-dependent increase in extracellular adenosine in hippocampal excitatory synapses, which can reach levels sufficient to block synaptic transmission. We now report that A2AR activation decreases A1R-medated inhibition of synaptic transmission, with particular relevance during high-frequency-induced long-term potentiation (LTP). Thus, whereas the A1R antagonist DPCPX (50 nM) was devoid of effects on LTP magnitude, the addition of an A2AR antagonist SCH58261 (50 nM) allowed a facilitatory effect of DPCPX on LTP to be revealed. Additionally, the activation of A2AR with CGS21680 (30 nM) decreased the potency o...
Neuroscience, 1995
A~ adenosine receptors efficiently modulate the excitatory synaptic transmission in hippocampus. Here we report that in addition to previously known modulatory action on the synaptic efficacy, A~ adenosine receptors are also capable of regulating the relative contribution of N-methyl-D-aspartate receptor-mediated component of the excitatory postsynaptic current in CA3-CA1 excitatory synapses, in the rat. When applied externally, a selective Al adenosine receptor antagonist, 8-cyclopentyl-l,3dimethylxanthine, increases not only the amplitude of excitatory postsynaptic current but also the relative contribution of the N-methyl-D-aspartate receptor-mediated component of postsynaptic current recorded by in situ voltage clamp. This effect develops only at increased external Ca 2+ concentration and also depends on the external Ca2+/Mg 2+ ratio. The increased ratio of N-methyl-D-aspartate/non-N-methyl-Daspartate components of excitatory postsynaptic current remains at a new level after the removal of 8-cyclopentyl-l,3-dimethylxanthine, even though the amplitude of excitatory postsynaptic current returns close to control value.
Neuroscience, 2002
AbstractöAdenosine tonically inhibits synaptic transmission through actions at A 1 receptors. It also facilitates synaptic transmission, but it is unclear if this facilitation results from pre-and/or postsynaptic A 2A receptor activation or from indirect control of inhibitory GABAergic transmission. The A 2A receptor agonist, CGS 21680 (10 nM), facilitated synaptic transmission in the CA1 area of rat hippocampal slices (by 14%), independent of whether or not GABAergic transmission was blocked by the GABA A and GABA B receptor antagonists, picrotoxin (50 WM) and CGP 55845 (1 WM), respectively. CGS 21680 (10 nM) also inhibited paired-pulse facilitation by 12%, an e¡ect prevented by the A 2A receptor antagonist, ZM 241385 (20 nM). These e¡ects of CGS 21680 (10 nM) were occluded by adenosine deaminase (2 U/ml) and were made to reappear upon direct activation of A 1 receptors with N 6 -cyclopentyladenosine (CPA, 6 nM). CGS 21680 (10 nM) only facilitated (by 17%) the K þ -evoked release of glutamate from superfused hippocampal synaptosomes in the presence of 100 nM CPA. This e¡ect of CGS 21680 (10 nM), in contrast to the isoproterenol (30 WM) facilitation of glutamate release, was prevented by the protein kinase C inhibitors, chelerythrine (6 WM) and bisindolylmaleimide (1 WM), but not by the protein kinase A inhibitor, H-89 (1 WM). Isoproterenol (30 WM), but not CGS 21680 (10^300 nM), enhanced synaptosomal cAMP levels, indicating that the CGS 21680-induced facilitation of glutamate release involves a cAMP-independent protein kinase C activation. To discard any direct e¡ect of CGS 21680 on adenosine A 1 receptor, we also show that in autoradiography experiments CGS 21680 only displaced the adenosine A 1 receptor antagonist, 1,3dipropyl-8-cyclopentyladenosine ([ 3 H]DPCPX, 0.5 nM) with an EC 50 of 1 WM in all brain areas studied and CGS 21680 (30 nM) failed to change the ability of CPA to displace DPCPX (1 nM) binding to CHO cells stably transfected with A 1 receptors.
Frontiers in Cellular Neuroscience, 2015
Adenosine is a widespread neuromodulator within the CNS and its extracellular level is increased during hypoxia or intense synaptic activity, modulating pre-and postsynaptic sites. We studied the neuromodulatory action of adenosine on glutamatergic currents in the hippocampus, showing that activation of multiple adenosine receptors (ARs) by basal adenosine impacts postsynaptic site. Specifically, the stimulation of both A 1 R and A 3 R reduces AMPA currents, while A 2A R has an opposite potentiating effect. The effect of ARs stimulation on glutamatergic currents in hippocampal cultures was investigated using pharmacological and genetic approaches. A 3 R inhibition by MRS1523 increased GluR1-Ser845 phosphorylation and potentiated AMPA current amplitude, increasing the apparent affinity for the agonist. A similar effect was observed blocking A 1 R with DPCPX or by genetic deletion of either A 3 R or A 1 R. Conversely, impairment of A 2A R reduced AMPA currents, and decreased agonist sensitivity. Consistently, in hippocampal slices, ARs activation by AR agonist NECA modulated glutamatergic current amplitude evoked by AMPA application or afferent fiber stimulation. Opposite effects of AR subtypes stimulation are likely associated to changes in GluR1 phosphorylation and represent a novel mechanism of physiological modulation of glutamatergic transmission by adenosine, likely acting in normal conditions in the brain, depending on the level of extracellular adenosine and the distribution of AR subtypes.