感官体验和学习会引起兴奋性和抑制性突触的持久变化,从而为存储器提供了关键的衬底。然而,兴奋性长时程增强(eLTP)或抑郁(eLTD)与抑制性突触同时变化(iLTP/iLTD)的协同调节仍不清楚.在这里,我们研究了NMDA诱导的突触可塑性的共表达在兴奋性和抑制性突触的海马CA1锥体细胞(PC)使用电生理,光遗传学,和药理学方法。我们发现,生长抑素(SST)和小白蛋白(PV)阳性中间神经元对CA1PC的抑制性输入在瞬时NMDA受体激活后显示出输入特异性的长期可塑性变化。值得注意的是,来自SST阳性中间神经元的突触一致表现出iLTP,与激发可塑性的方向无关,而来自PV阳性中间神经元的突触主要显示iLTP与eLTP并发,而不是eLTD。已知神经可塑性依赖于细胞外基质,我们测试了金属蛋白酶(MMP)抑制的影响。MMP3阻断干扰了所有抑制性输入的GABA能可塑性,而MMP9抑制选择性阻断与eLTP共同发生的SST-CA1PC突触中的eLTP和iLTP,而不阻断eLTP。这些发现证明了兴奋性和抑制性可塑性共表达的解离。我们认为这些可塑性共表达的机制可能与维持兴奋-抑制平衡和调节神经元整合模式有关。
Sensory experiences and learning induce long-lasting changes in both excitatory and inhibitory synapses, thereby providing a crucial substrate for memory. However, the co-tuning of excitatory long-term potentiation (eLTP) or depression (eLTD) with the simultaneous changes at inhibitory synapses (iLTP/iLTD) remains unclear. Herein, we investigated the co-expression of NMDA-induced synaptic plasticity at excitatory and inhibitory synapses in hippocampal CA1 pyramidal cells (PCs) using a combination of electrophysiological, optogenetic, and pharmacological approaches. We found that inhibitory inputs from somatostatin (SST) and parvalbumin (PV)-positive
interneurons onto CA1 PCs display input-specific long-term plastic changes following transient NMDA receptor activation. Notably, synapses from SST-positive
interneurons consistently exhibited iLTP, irrespective of the direction of excitatory plasticity, whereas synapses from PV-positive
interneurons predominantly showed iLTP concurrent with eLTP, rather than eLTD. As neuroplasticity is known to depend on the extracellular matrix, we tested the impact of metalloproteinases (MMP) inhibition. MMP3 blockade interfered with GABAergic plasticity for all inhibitory inputs, whereas MMP9 inhibition selectively blocked eLTP and iLTP in SST-CA1PC synapses co-occurring with eLTP but not eLTD. These findings demonstrate the dissociation of excitatory and inhibitory plasticity co-expression. We propose that these mechanisms of plasticity co-expression may be involved in maintaining excitation-inhibition balance and modulating neuronal integration modes.