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ATP derived from astrocytes modulates memory in the chick

Published online by Cambridge University Press:  06 July 2012

Marie E. Gibbs*
Affiliation:
Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia
Maria Shleper
Affiliation:
Florey Neurosciences Institute, University of Melbourne, Victoria, Australia
Tomris Mustafa
Affiliation:
Florey Neurosciences Institute, University of Melbourne, Victoria, Australia
Geoffrey Burnstock
Affiliation:
Autonomic Neuroscience Centre, University College Medical School, London, UK
David N. Bowser
Affiliation:
Florey Neurosciences Institute, University of Melbourne, Victoria, Australia
*
Correspondence should be addressed to: Marie E. Gibbs, Monash Institute of Pharmaceutical Sciences, 399 Royal Parade, Parkville, Victoria 3052, Australia email: marie.gibbs@monash.edu

Abstract

Memory consolidation in a discriminative bead pecking task is modulated by endogenous adenosine triphosphate (ATP) acting at purinergic receptors in the hippocampus. Consolidation, from short- to intermediate- to long-term memory during two distinct periods following training, was blocked by the non-selective P2 purinergic receptor antagonist PPADS (pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) tetrasodium salt hydrate and the specific P2Y1 receptor antagonist MRS2179. Direct injections of the ATP agonists (ATPγS and ADPβS) potentiated memory consolidation and the effect of ADPβS was blocked by MRS2179, suggesting an important role of ATP on memory consolidation via the P2Y1 receptor in the chick hippocampus. Incubation of astrocytes with ATPγS and ADPβS resulted in the increase of intracellular calcium ([Ca2+]i), the latter being blocked by MRS2179 suggesting a specific role for P2Y1 receptors in the calcium response. This response was prevented by blocking astrocytic oxidative metabolism with fluoroacetate. We argue that the source of the ATP acting on neuronal P2Y1 receptors is most likely to be astrocytes. Thrombin selectively increases [Ca2+]i in astrocytes but not in neurones. The main findings of the present study are: (a) astrocytic [Ca2+]i plays an important role in the consolidation of short-term to long-term memory; and (b) ATP released from chick astrocytes during learning modulates neuronal activity through astrocytic P2Y1 receptors.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2012

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