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.
Masino1, 2 and
Thomas V.
Dunwiddie1, 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
Copyright © 1999 Society for Neuroscience 0270-6474/99/1961932-08$05.00/0
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