HOMOSYNAPTIC LONG-TERM DEPRESSION IN AREA CA1 OF HIPPOCAMPUS AND EFFECTS OF N-METHYL-D-ASPARTATE RECEPTOR BLOCKADE
HOMOSYNAPTIC LONG-TERM DEPRESSION IN AREA CA1 OF HIPPOCAMPUS AND EFFECTS OF N-METHYL-D-ASPARTATE RECEPTOR BLOCKADE
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DOI：
10.1073/pnas.89.10.4363
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发表时间：
1992-05-15
影响因子：
11.1
通讯作者：
BEAR, MF
中科院分区：
文献类型：
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作者：
DUDEK, SM;BEAR, MF
我们测试了一个理论上的预测，即兴奋性输入活性的模式始终无法充分激活靶神经元以诱导突触增强，而将导致特定的突触抑制。为了实验实现这种情况，在大鼠海马切片中的Schaffer侧支投影在0.5至50 Hz的频率下进行电刺激。 1-3 Hz时的900个脉冲始终产生CA1种群兴奋性突触后潜能的抑郁症，在停止调节刺激后持续持续没有恢复> 1小时的迹象。这种长期抑郁症是针对条件投入的特定的，排除了突触后反应性或兴奋性的广义变化。三条证据表明，这种影响是通过修改突触有效性而不是对刺激输入的损害或疲劳来解释的。首先，效果取决于刺激频率。在10 Hz时的900脉冲没有持久变化，通常在50 Hz时观察到突触增强。其次，抑郁的突触继续支持长期增强，以响应高频破伤风。第三，通过应用NMDA受体拮抗剂可以预防调节刺激的影响。因此，我们的数据表明，突触抑郁症可以由延长的NMDA受体激活触发，该激活低于诱导突触增强的阈值。我们建议这种机制对于基于某些形式的学习和记忆的海马反应特性的修改很重要。
We tested a theoretical prediction that patterns of excitatory input activity that consistently fail to activate target neurons sufficiently to induce synaptic potentiation will instead cause a specific synaptic depression. To realize this situation experimentally, the Schaffer collateral projection to area CA1 in rat hippocampal slices was stimulated electrically at frequencies ranging from 0.5 to 50 Hz. Nine hundred pulses at 1-3 Hz consistently yielded a depression of the CA1 population excitatory postsynaptic potential that persisted without signs of recovery for > 1 hr after cessation of the conditioning stimulation. This long-term depression was specific to the conditioned input, ruling out generalized changes in postsynaptic responsiveness or excitability. Three lines of evidence suggest that this effect is accounted for by a modification of synaptic effectiveness rather than damage to or fatigue of the stimulated inputs. First, the effect was dependent on the stimulation frequency; 900 pulses at 10 Hz caused no lasting change, and at 50 Hz a synaptic potentiation was usually observed. Second, the depressed synapses continued to support long-term potentiation in response to a high-frequency tetanus. Third, the effects of conditioning stimulation could be prevented by application of NMDA receptor antagonists. Thus, our data suggest that synaptic depression can be triggered by prolonged NMDA receptor activation that is below the threshold for inducing synaptic potentiation. We propose that this mechanism is important for the modifications of hippocampal response properties that underlie some forms of learning and memory.