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

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.

Duke Scholars

Author Darrell Vincent Lewis Jr. Pediatrics, Neurology