Masking of forskolin-induced long-term potentiation by adenosine accumulation in area CA1 of the rat hippocampus

Kwok Tung Lu, Po Wu Gean

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

At hippocampal Schaffer collateral-CA1 synapses, activation of β- adrenergic receptors and adenylyl cyclase increases transmitter release. However, this effect is transient, which is in contrast to that seen at mossy fiber-CA3 synapses, where activation of cyclic-AMP-dependent protein kinase results in long-lasting facilitation of transmitter release, a phenomenon known as a presynaptic form of long-term potentiation. The present study was aimed at investigating whether forskolin, an adenylyl cyclase activator, could produce long-term effects at the Schaffer collateral-CAl synapses using extracellular recording techniques. As has been reported previously, forskolin persistently increased the amplitude of evoked population spikes without having a long-term effect on the field excitatory postsynaptic potentials. However, under the conditions where adenosine A 1 receptors are inhibited, cyclic-AMP metabolism is disrupted or the transport of cyclic-AMP is blocked, forskolin induces long-term potentiation. Forskolin-induced potentiation is associated with a decrease in paired-pulse facilitation and is blocked by the cyclic-AMP-dependent protein kinase inhibitor Rp-adenosine- 3',5'-cyclic monophosphorothioate. Activation of N-methyl-D-aspartate receptors is not required for forskolin-induced long-term potentiation, because pretreatment of slices with the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovalerate did not prevent forskolin-induced potentiation. These results suggest that blockade of adenosine A 1 receptors unmasks forskolin-induced long-term potentiation, and activation of cyclic- AMP-dependent protein kinase induces a form of long-term potentiation which is different from that induced by tetanic stimulation.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalNeuroscience
Volume88
Issue number1
DOIs
Publication statusPublished - 1999 Jan 1

Keywords

  • Adenosine
  • CAMP
  • Forskolin
  • Hippocampus
  • Long-term potentiation
  • Protein kinase A

ASJC Scopus subject areas

  • Neuroscience(all)

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