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The Journal of Neuroscience, March 15, 1999, 19(6):1932-1939

Temperature-Dependent Modulation of Excitatory Transmission in Hippocampal Slices Is Mediated by Extracellular Adenosine

Susan A. Masino^{1, 2} and Thomas V. Dunwiddie^{1, 2, 3}

¹ Neuroscience Program and ² Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, and ³ Veterans Affairs Medical Research Service, Denver, Colorado 80220

Although extracellular adenosine concentrations in brain are increased markedly by a variety of stimuli such as hypoxia and ischemia, it has been difficult to demonstrate large increases in adenosine with stimuli that do not result in pathological tissue damage. The present studies demonstrate that increasing the temperature at which rat hippocampal brain slices are maintained (typically from 32.5 to 38.5°C) markedly inhibits excitatory synaptic transmission. This effect was reversible on cooling, readily repeatable, and was blocked by A₁ receptor antagonists and by adenosine deaminase, suggesting that it was mediated by increased activation of presynaptic adenosine A₁ receptors by endogenous adenosine. This increase in adenosinergic inhibition was not a response to hyperthermia per se, because it could be elicited by temperatures that remained entirely within the hypothermic range (e.g., from 32.5 to 35.5°C). The increased activity at A₁ receptors appeared to be attributable to the direct release of adenosine via nucleoside transporters; the release of adenine nucleotides, linked to either the activation of NMDA receptors or the increased efflux of cAMP, appeared not to be involved. These results suggest that changes in brain temperature can alter the regulation of extracellular adenosine in rat brain slices and that increased adenosine release may be an important regulatory mechanism for countering increased excitability consequent to increased brain temperature.

Key words: adenosine; hippocampus; temperature; hyperthermia; A₁ receptors; CA1

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1961932-08$05.00/0

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