Increased adenosine levels in mice expressing mutant glial fibrillary acidic protein in astrocytes result in failure of induction of LTP reversal (depotentiation) in hippocampal CA1 neurons

Satoshi Fujii, Kenji Tanaka, Kazuhiro Ikenaka, Yoshihiko Yamazaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Astrocytes regulate the activity of neighboring neurons by releasing chemical transmitters, including ATP. Adenosine levels in the cerebrospinal fluidof mice thatexpress amutanthuman glial fibrillary acidic protein in astrocytes are slightly elevated compared to those in wild type mice and this might result from the observed increased release by mutant astrocytes of ATP, which can be used to produce adenosine. Using hippocampal slices from these mutant mice, we examined whether the increased endogenous adenosine levels in the hippocampus modulate the reversal of long-term potentiation (LTP), i.e. depotentiation (DP), in CA1 neurons. In hippocampal slices from wild type mice, a stable LTP was induced by tetanic stimulation consisting of 100 pulses at 100 Hz, and this was reversed by a train of low frequency stimulation (LFS) of 500 pulses at 1 Hz applied 30 min later. This induction of DP was inhibited by application of either 100 nM adenosine or 0.5 nM N6-cyclopentyladenosine, an adenosine A1 receptor agonist, during LFS, indicating that the increase in extracellular adenosine levels attenuated DP induction by acting on adenosine A1 receptors. In contrast, although a stable LTP was also induced in hippocampal slices from mutant mice, induction of DP was inhibited, but DP could be induced by application, during LFS, of 50 nM 8-cyclopentyltheophylline, an adenosine A1 receptor antagonist. These results suggest that a small increase in extracellular adenosine levels resulting from increased ATP release by astrocytes resultsinattenuationofDPinhippocampal CA1neurons inthemutantmice.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalBrain Research
Volume1578
Issue number1
DOIs
Publication statusPublished - 2014

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Long-Term Synaptic Depression
Long-Term Potentiation
Glial Fibrillary Acidic Protein
Mutant Proteins
Astrocytes
Adenosine
Neurons
Adenosine Triphosphate
Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists
Adenosine A1 Receptors
Hippocampus

Keywords

  • Adenosine
  • Astrocyte LTP
  • ATP
  • Depotentiation Hippocampus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Increased adenosine levels in mice expressing mutant glial fibrillary acidic protein in astrocytes result in failure of induction of LTP reversal (depotentiation) in hippocampal CA1 neurons. / Fujii, Satoshi; Tanaka, Kenji; Ikenaka, Kazuhiro; Yamazaki, Yoshihiko.

In: Brain Research, Vol. 1578, No. 1, 2014, p. 1-13.

Research output: Contribution to journalArticle

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