Mott D D, Lewis D V
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Epilepsy Res Suppl. 1992;7:119-34.
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.
我们研究了突触抑制在调节大鼠海马切片齿状回中长时程增强（LTP）发育中的作用。通过以5Hz的频率对分子层进行重复刺激来产生LTP，该频率处于θ节律范围内。在这种重复刺激期间，反应变得更宽并出现额外的群体峰电位。这种增强是由反应中N-甲基-D-天冬氨酸（NMDA）成分的增加引起的。NMDA反应增强是因为潜在的γ-氨基丁酸-A（GABAA）受体介导的抑制性突触后电位（IPSP）受到抑制。应用2-羟基氯苯氨丁酸可防止IPSP的抑制以及NMDA成分的增加，表明NMDA反应的增强是由GABAB受体介导的抑制作用抑制所致。此外，通过阻止GABAB受体介导的去抑制作用，从而阻止NMDA成分的增加，2-羟基氯苯氨丁酸在刺激序列后阻断了LTP的发展。这些观察结果表明，GABAB受体介导的去抑制作用是5Hz刺激诱导LTP所必需的，并表明GABAB受体代表了调节突触可塑性的一个新位点。这些现象在完整海马体中的可能功能意义值得研究。
