Poor correlation between postsynaptic [Ca]i increases and long-term potentiation induced by 2-deoxyglucose in CA1 hippocampal neurons

K. Krnjevic, S. Tekkök, I. Medina, Y. T. Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

2-Deoxyglucose (2-DG; 10 mM) replacing glucose for ≈15 min regularly causes a very sustained enhancement of synaptic transmission in the CA1 hippocampal zone (2-DG-induced long-term potentiation, 2-DG-LTP). This LTP is prevented by dantrolene (10 μM) or by the NMDA antagonist aminophosphonovalerate (APV; 50-100 μM); it is Ca-dependent [1, 2], and is not depressed by adenosine antagonists (DPCPX and 8-SPT), which prevent the initial block of EPSP caused by 2-DG, but is not observed if glucose is replaced by sucrose instead of 2-DG. To clarify the role of [Ca]i in 2-DG-LTP, we monitored fluo-3 fluorescence In CA1 neurons, in submerged slices kept at 30°C. 2-DG applied as above consistently led to a rapid, but reversible rise in fluorescence. Isomolar sucrose (for 15-40 min) elicited smaller, but significant increases in fluorescence. Dantrolene and APV greatly reduced 2-DG's effect, but Ca-free medium did not abolish it. Paradoxically, it was fully suppressed by 8-SPT, but not at all by DPCPX. The discrepancies between the effects of sucrose and 8-SPT on the fluorescence changes and on 2-DG-LTP suggest that the observed increases in the postsynaptic [Ca]i are not essential for 2-DG-LTP. In further experiments, intracellular recordings showed that 2-DG applications consistently hyperpolarize CA1 neurons, probably owing to adenosine-mediated activation of K+ conductance (which could be prevented by DPCPX or 8-SPT, but not by a KATP antagonist, glyburide). The 2-DG-LTP of EPSP was not suppressed by EGTA leakage from electrodes, in keeping with the above evidence that the [Ca]i changes needed for the induction of 2-DG-LTP are not those observed postsynaptically. In this respect, as well as in the absence of postsynaptic depolarization, 2-DG-LTP offers a marked contrast to more conventional forms of LTP.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalNeurophysiology
Volume29
Issue number4-5
DOIs
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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