Wagner J J, Alger B E
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
J Neurosci. 1995 Feb;15(2):1577-86. doi: 10.1523/JNEUROSCI.15-02-01577.1995.
Low-frequency (1 Hz) stimulation (LFS) was used to elicit long-term depression (LTD) or depotentiation of excitatory transmission of the Schaffer collateral pathway in the CA1 region of the rat hippocampus. Both LTD and depotentiation were found to be homosynaptic and NMDA receptor (NMDAR) dependent. As NMDAR activation can be modulated by the inhibitory GABAergic system, we tested the hypothesis that GABA plays a role in regulating these phenomena. The GABAB antagonist CGP 35348 significantly inhibited LTD, but not depotentiation, in slices from young animals (indicating that the GABAB-mediated contribution was altered following HFS). The ability to express LTD was found to be developmentally dependent, as young animals (16-22 d) consistently expressed LTD, whereas LTD was not expressed in naive slices taken from mature (5-10 weeks) animals. The GABAA antagonist bicuculline did not affect LTD in the young animals, but did enhance LTD expression in slices from mature animals. LFS was also effective in decreasing, or depotentiating, responses that had undergone long-term potentiation (LTP) by high-frequency stimulation (HFS). In contrast to LTD, depotentiation was consistently expressed in slices from both the young and mature groups. Moreover, following an HFS train, LTD (compared to initial baseline response) could be induced in mature slices previously unable to express LTD in the naive state. Thus, the role of GABA in modulating the effects of LFS varied with the prior synaptic activity in the slice as well as with the maturity of the animal. Our results suggest that the influence of both age and prior synaptic activity (i.e., HFS) on LTD induction can be explained by changes in GABAergic systems in young versus mature, and naive versus tetanized slices.
采用低频（1赫兹）刺激（LFS）来诱发大鼠海马CA1区Schaffer侧支通路兴奋性传递的长时程抑制（LTD）或去增强。发现LTD和去增强均为同突触且依赖N-甲基-D-天冬氨酸受体（NMDAR）。由于NMDAR的激活可受抑制性γ-氨基丁酸（GABA）能系统调节，我们检验了GABA在调节这些现象中起作用的假说。GABAB拮抗剂CGP 35348显著抑制幼龄动物脑片的LTD，但不影响去增强（表明高频刺激（HFS）后GABAB介导的作用发生了改变）。发现表达LTD的能力具有发育依赖性，因为幼龄动物（16 - 22日龄）始终能表达LTD，而从成熟（5 - 10周龄）动物获取的未经处理的脑片中不表达LTD。GABAA拮抗剂荷包牡丹碱不影响幼龄动物的LTD，但能增强成熟动物脑片的LTD表达。LFS对通过高频刺激（HFS）产生长时程增强（LTP）的反应也有降低或去增强作用。与LTD不同，幼龄组和成熟组脑片均能持续表达去增强。此外，在HFS串刺激后，先前在未经处理状态下不能表达LTD的成熟脑片中可诱导出LTD（与初始基线反应相比）。因此，GABA在调节LFS作用方面的作用随脑片先前的突触活动以及动物的成熟度而变化。我们的结果表明，年龄和先前突触活动（即HFS）对LTD诱导的影响可通过幼龄与成熟、未经处理与强直刺激脑片中GABA能系统的变化来解释。
