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.
Mott
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DD
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Lewis
D V
DV
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D046508:Culture Techniques; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000145:classification / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013826:Theta Rhythm
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate