Continuous blockade of GABA-ergic inhibition induces novel forms of long-lasting plastic changes in apical dendrites of the hippocampal cornu ammonis 1 (CA1) in vitro

J. U. Frey

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Hippocampal long-term potentiation (LTP) is considered as a fundamental mechanism for learning and memory formation. A role for GABA was reported for the induction and early but not late maintenance of LTP. We have now investigated whether GABA-receptor function is involved in the prolonged maintenance of LTP (>4 h) at afferent synapses at apical dendrites of cornu ammonis 1 (CA1)-pyramidal neurons in hippocampal slices in vitro. Our data demonstrate that GABA-receptor mediated events are not required for conventional, tetanically-induced early- or late-LTP in the hippocampal CA1-region in vitro. Inhibition of GABA-ergic transmission did not negatively influence either early- or late-LTP. In contrast, an additional facilitation was observed at time points corresponding to the establishment of late-LTP (after 3-4 h). Investigation of a second, non-tetanized control input to the same neuronal population revealed that the elevated potentiation of late-LTP in the tetanized input was not LTP-specific. Therefore, we have examined, whether continuous application of GABA-receptor inhibitors also affected the time course of the recorded potentials when a low-frequency stimulation protocol was used. Under these conditions two distinct forms of a late-onset potentiation occurred 5-6 h after drug application. Investigation of mechanisms responsible for this prolonged enhancement of potentials revealed that the higher form of potentiation (potentiation levels above 200%) was dependent on presynaptic activity and N-methyl-d-aspartate (NMDA)-receptor activation, whereas the lower form (potentiation less than 200%) did not require these mechanisms. However, the latter potentiation was prevented by nifedipine, an L-type voltage-dependent calcium channel inhibitor.

Original languageEnglish (US)
Pages (from-to)188-197
Number of pages10
JournalNeuroscience
Volume165
Issue number1
DOIs
StatePublished - Jan 13 2010

Keywords

  • early- and late-LTP
  • epilepsy
  • GABA
  • hippocampal slice in vitro
  • long-term potentiation
  • synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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