Anisimova Margarita, van Bommel Bas, Wang Rui, Mikhaylova Marina, Wiegert Jörn Simon, Oertner Thomas G, Gee Christine E
Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Falkenried 94, D-20251 Hamburg, Germany.
Institute for Chemistry and Biochemistry, Feie Universität Berlin, Berlin, Germany.
Cereb Cortex. 2022 Dec 15;33(1):23-34. doi: 10.1093/cercor/bhac050.
Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain, but the whole-cell recordings required for the experimental induction of STDP are typically limited to 1 h. This mismatch of time scales is a long-standing weakness in synaptic theories of memory. Here we use spectrally separated optogenetic stimulation to fire precisely timed action potentials (spikes) in CA3 and CA1 pyramidal cells. Twenty minutes after optogenetic induction of STDP (oSTDP), we observed timing-dependent depression (tLTD) and timing-dependent potentiation (tLTP), depending on the sequence of spiking. As oSTDP does not require electrodes, we could also assess the strength of these paired connections three days later. At this late time point, late tLTP was observed for both causal (CA3 before CA1) and anticausal (CA1 before CA3) timing, but not for asynchronous activity patterns (Δt = 50 ms). Blocking activity after induction of oSTDP prevented stable potentiation. Our results confirm that neurons wire together if they fire together, but suggest that synaptic depression after anticausal activation (tLTD) is a transient phenomenon.
尖峰时间依赖性可塑性（STDP）是大脑中信息存储的一种潜在机制，但实验诱导STDP所需的全细胞记录通常限于1小时。这种时间尺度的不匹配是记忆突触理论中长期存在的一个弱点。在这里，我们使用光谱分离的光遗传学刺激在CA3和CA1锥体细胞中精确激发定时动作电位（尖峰）。在光遗传学诱导STDP（oSTDP）20分钟后，我们观察到了时间依赖性抑制（tLTD）和时间依赖性增强（tLTP），这取决于尖峰的顺序。由于oSTDP不需要电极，我们还可以在三天后评估这些配对连接的强度。在这个较晚的时间点，对于因果性（CA3在CA1之前）和反因果性（CA1在CA3之前）的时间顺序都观察到了晚期tLTP，但对于异步活动模式（Δt = 50毫秒）则没有。在诱导oSTDP后阻断活动会阻止稳定的增强。我们的结果证实，如果神经元同时放电，它们会连接在一起，但表明反因果激活后的突触抑制（tLTD）是一种短暂现象。
