GABAB receptors mediate disinhibition and facilitate long-term potentiation in the dentate gyrus.

Journal Article (Journal Article)

We examined the role of synaptic inhibition in regulating the development of long-term potentiation (LTP) in the dentate gyrus of the rat hippocampal slice. LTP was produced by delivering repetitive stimulation to the molecular layer at 5 Hz, a frequency in the range of theta rhythm. During this repetitive stimulation, responses became wider and developed extra population spikes. This enhancement was caused by an increase in the N-methyl-D-aspartate (NMDA) component of the response. NMDA responses became enhanced because there was suppression of the underlying gamma-aminobutyric acid-A (GABAA) receptor-mediated inhibitory postsynaptic potential (IPSP). Application of 2-OH saclofen prevented both the suppression of the IPSP as well as the increase in the NMDA component, demonstrating that the enhancement of the NMDA response was caused by a GABAB receptor-mediated suppression of inhibition. Furthermore, by preventing the GABAB receptor-mediated disinhibition, and thus the increase in the NMDA component, 2-OH saclofen blocked the development of LTP following the stimulus train. These observations indicate that GABAB receptor-mediated disinhibition is required for LTP induction by 5-Hz stimulation, and suggest that GABAB receptors represent a novel site for modulation of synaptic plasticity. The possible functional significance of these phenomena in the intact hippocampal deserves to be investigated.

Full Text

Duke Authors

Cited Authors

  • Mott, DD; Lewis, DV

Published Date

  • 1992

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 119 - 134

PubMed ID

  • 1334658

International Standard Serial Number (ISSN)

  • 0922-9833


  • eng

Conference Location

  • Netherlands