Huang Chiung-Chun, Hsu Kuei-Sen
Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, Ta-Hsiue Road, Tainan 701, Taiwan.
J Physiol. 2004 Nov 15;561(Pt 1):91-108. doi: 10.1113/jphysiol.2004.072546. Epub 2004 Sep 2.
Reversal of long-term potentiation (LTP) by long trains of low-frequency stimulation is generally referred to as depotentiation. One of the intriguing aspects of depotentiation is that the magnitude of depotentiation is inversely proportional to the time lag of depotentiation stimulation following LTP induction. Although the mechanisms underlying depotentiation have been widely explored, the factors that regulate the susceptibility of LTP to depotentiation stimulation remain largely unclear. We now report that multiple trains of high-frequency stimulation provide immediate synaptic resistance to depotentiation stimulation at the mossy fibre-CA3 synapses. The synaptic resistance to depotentiation stimulation depends on the amount of synaptic stimulation used to induce LTP; it is prevented by protein synthesis inhibitors and is input specific. In contrast, neither the transection of mossy fibre axons near granule cell somata nor the application of RNA synthesis inhibitors influences synaptic resistance to depotentiation stimulation. We also provide evidence that the induction of depotentiation is regulated by GABA(B) receptors. Application of a GABA(B) receptor antagonist significantly promoted the synaptic resistance to depotentiation stimulation, whereas inhibition of GABA transport delayed the onset of this synaptic resistance. These results suggest that local protein synthesis is required for the development of synaptic resistance to depotentiation stimulation, whereas the activation of GABA(B) receptors promotes the susceptibility to depotentiation stimulation. These two factors may crucially regulate the reversal and stability of long-term information storage.
通过长时间的低频刺激来逆转长时程增强（LTP）通常被称为去增强。去增强的一个有趣之处在于，去增强的幅度与LTP诱导后去增强刺激的时间间隔成反比。尽管去增强的潜在机制已被广泛探索，但调节LTP对去增强刺激敏感性的因素仍 largely不清楚。我们现在报告，多串高频刺激在苔藓纤维-CA3突触处为去增强刺激提供了即时的突触抗性。对去增强刺激的突触抗性取决于用于诱导LTP的突触刺激量；它被蛋白质合成抑制剂所阻止，并且具有输入特异性。相比之下，在颗粒细胞胞体附近切断苔藓纤维轴突以及应用RNA合成抑制剂均不影响对去增强刺激的突触抗性。我们还提供证据表明，去增强的诱导受GABA(B)受体调节。应用GABA(B)受体拮抗剂显著促进了对去增强刺激的突触抗性，而抑制GABA转运则延迟了这种突触抗性的出现。这些结果表明，局部蛋白质合成是对去增强刺激产生突触抗性所必需的，而GABA(B)受体的激活促进了对去增强刺激的敏感性。这两个因素可能对长期信息存储的逆转和稳定性起着关键调节作用。
