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The mechanism of electrically stimulated adenosine release varies by brain region

Abstract

Adenosine plays an important role in neuromodulation and neuroprotection. Recent identification of transient changes in adenosine concentration suggests adenosine may have a rapid modulatory role; however, the extent of these changes throughout the brain is not well understood. In this report, transient changes in adenosine evoked by one second, 60 Hz electrical stimulation trains were compared in the caudate–putamen, nucleus accumbens, hippocampus, and cortex. The concentration of evoked adenosine varies between brain regions, but there is less variation in the duration of signaling. The highest concentration of adenosine was evoked in the dorsal caudate–putamen (0.34 ± 0.08 μM), while the lowest concentration was in the secondary motor cortex (0.06 ± 0.02 μM). In all brain regions, adenosine release was activity-dependent. In the nucleus accumbens, hippocampus, and prefrontal cortex, this release was partly due to extracellular ATP breakdown. However, in the caudate–putamen, release was not due to ATP metabolism but was ionotropic glutamate receptor-dependent. The results demonstrate that transient, activity-dependent adenosine can be evoked in many brain regions but that the mechanism of formation and release varies by region.

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Abbreviations

FSCV:

fast-scan cyclic voltammetry

aCSF:

artificial cerebrospinal fluid

EDTA:

ethylenediaminetetraacetic acid

TTX:

tetrodotoxin

AOPCP:

α,β-methylene adenosine diphosphate

CNQX:

6-cyano-7-nitroquinoxaline-2,3-dione

AP5:

D(−)-2-amino-5-phosphonopentanoic acid

CP:

caudate-putamen

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Acknowledgments

The authors have no conflict of interest related to this research. Funding for this research was provided by the National Institute of Health R01NS076875 and the University of Virginia.

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Correspondence to B. Jill Venton.

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Pajski, M.L., Venton, B.J. The mechanism of electrically stimulated adenosine release varies by brain region. Purinergic Signalling 9, 167–174 (2013). https://doi.org/10.1007/s11302-012-9343-2

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Keywords

  • Carbon-fiber microelectrode
  • Striatum
  • Hippocampus
  • Cortex
  • Electrical stimulation
  • Fast-scan cyclic voltammetry