Purinergic P2X, P2Y and adenosine receptors differentially modulate hippocampal gamma oscillations.

Steffen B Schulz, Zin-Juan Klaft, Anton R Rösler, Uwe Heinemann, Zoltan Gerevich

Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Oudenarder Str. 16, D-13347 Berlin, Germany.

Neuropharmacology 2012 Feb

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The present study was designed to investigate the role of extracellular ATP and its receptors on neuronal network activity. Gamma oscillations (30-50 Hz) were induced in the CA3 region of acute rat hippocampal slices by either acetylcholine (ACh) or kainic acid (KA). ATP reduced the power of KA-induced gamma oscillations exclusively by activation of adenosine receptors after its degradation to adenosine. In contrast, ATP suppressed ACh-induced oscillations through both adenosine and ATP receptors. Activation of adenosine receptors accounts for about 55%, activation of P2 receptors for ∼45% of suppression. Monitoring the ATP degradation by ATP biosensors revealed that bath-applied ATP reaches ∼300 times lower concentrations within the slice. P2 receptors were also activated by endogenous ATP since inhibition of ATP-hydrolyzing enzymes had an inhibitory effect on ACh-induced gamma oscillations. More specific antagonists revealed that ionotropic P2X2 and/or P2X4 receptors reduced the power of ACh-induced gamma oscillations whereas metabotropic P2Y(1) receptor increased it. Intracellular recordings from CA3 pyramidal cells suggest that adenosine receptors reduce the spiking rate and the synchrony of action potentials during gamma oscillations whereas P2 receptors only modulate the firing rate of the cells. In conclusion, our results suggest that endogenously released ATP differentially modulates the power of ACh- or KA-induced gamma oscillations in the CA3 region of the hippocampus by interacting with P2X, P2Y and adenosine receptors. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Citation

Steffen B Schulz, Zin-Juan Klaft, Anton R Rösler, Uwe Heinemann, Zoltan Gerevich. Purinergic P2X, P2Y and adenosine receptors differentially modulate hippocampal gamma oscillations. Neuropharmacology. 2012 Feb;62(2):914-24