Department of Biophysics and Neuroscience, Wroclaw Medical University, 3a Chalubinskiego Str., 50-368, Wroclaw, Poland.
Sci Rep. 2024 Sep 3;14(1):20463. doi: 10.1038/s41598-024-70278-w.
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.
感觉体验和学习会在兴奋性和抑制性突触中诱导长期变化，从而为记忆提供重要的基础。然而，兴奋性长时程增强（eLTP）或抑制性长时程抑制（iLTD）的同时变化与抑制性突触的同时调节（iLTP/iLTD）之间的共同调节仍不清楚。在此，我们使用电生理学、光遗传学和药理学方法的组合，研究了海马 CA1 锥体神经元（PC）中 NMDA 诱导的突触可塑性在兴奋性和抑制性突触中的共同表达。我们发现，来自生长抑素（SST）和小清蛋白（PV）阳性中间神经元的抑制性输入在短暂 NMDA 受体激活后，对 CA1 PC 显示出具有输入特异性的长期可塑性变化。值得注意的是，SST 阳性中间神经元的突触始终表现出 iLTP，而与兴奋性可塑性的方向无关，而 PV 阳性中间神经元的突触主要表现出与 eLTP 同时发生的 iLTP，而不是 eLTD。由于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可塑性，而 MMP9 抑制选择性地阻断了 SST-CA1PC 突触的 eLTP 和 iLTP，而不阻断 eLTD。这些发现表明兴奋性和抑制性可塑性的共同表达是分离的。我们提出，这些可塑性共同表达的机制可能参与维持兴奋-抑制平衡和调节神经元整合模式。
