Changed NMDA receptor (NMDAr) physiology is implicated with cognitive deficit resulting from conditions ranging from normal aging to neurological disease. Using intermittent hypoxia (IH) to experimentally model untreated sleep apnea, a clinical condition whose comorbidities include neurocognitive impairment, we recently demonstrated that IH causes a pro-oxidant condition that contributes to deficits in spatial memory and in NMDAr-dependent long-term potentiation (LTP). However, the impact of IH on additional forms of synaptic plasticity remains ill-defined. Here we show that IH prevents the induction of NMDAr-dependent LTP and long-term depression (LTD) in hippocampal brain slices from mice exposed to ten days of IH (IH₁₀) yet spares NMDAr-independent forms of synaptic plasticity. Deficits in synaptic plasticity were accompanied by a reduction in hippocampal GluN1 expression. Acute manipulation of redox state using the reducing agent, Dithiothreitol (DTT) stimulated the NMDAr-dependent fEPSP following IH₁₀. However, acute use of either DTT or MnTMPyP did not restore NMDAr-dependent synaptic plasticity after IH₁₀ or prevent the IH-dependent reduction in GluN1, the obligatory subunit of the NMDAr. In contrast, MnTMPyP during IH₁₀ (10-MnTMPyP), prevented the suppressive effects of IH on both NMDAr-dependent synaptic plasticity and GluN1 expression. These findings indicate that while the IH-dependent pro-oxidant state causes reversible oxidative neuromodulation of NMDAr activity, acute manipulation of redox state is ineffective in rescuing two key effects of IH related to the NMDAr within the hippocampus. These IH-dependent changes associated with the NMDAr may be a primary avenue by which IH enhances the vulnerability to impaired learning and memory when sleep apnea is left untreated in normal aging and in disease.

改变的 NMDA 受体 (NMDAr) 生理学与从正常衰老到神经系统疾病的各种状况导致的认知缺陷有关。使用间歇性缺氧 (IH) 对未经治疗的睡眠呼吸暂停（一种伴随神经认知障碍的临床病症）进行实验建模，我们最近证明 IH 会导致促氧化状况，导致空间记忆缺陷和 NMDAr 依赖性长时程增强。 LTP）。然而，IH 对其他形式的突触可塑性的影响仍然不明确。在这里，我们表明 IH 可防止暴露于 IH 十天（IH ₁₀) 但保留了与 NMDAr 无关的突触可塑性形式。突触可塑性的缺陷伴随着海马 GluN1 表达的减少。_{使用还原剂二硫苏糖醇 (DTT) 对氧化还原状态的急性操作刺激了 IH 10}后依赖 NMDAr 的 fEPSP 。然而，急性使用 DTT 或 MnTMPyP 并不能在 IH ₁₀后恢复 NMDAr 依赖性突触可塑性或阻止 NMDAr 的强制性亚基 GluN1 的 IH 依赖性减少。相比之下，IH _{10期间的 MnTMPyP}(10-MnTMPyP)，阻止 IH 对 NMDAr 依赖性突触可塑性和 GluN1 表达的抑制作用。这些发现表明，虽然 IH 依赖的促氧化状态导致 NMDAr 活性的可逆氧化神经调节，但氧化还原状态的急性操纵在挽救与海马内 NMDAr 相关的 IH 的两个关键效应方面无效。这些与 NMDAr 相关的 IH 依赖性变化可能是当在正常衰老和疾病中未治疗睡眠呼吸暂停时，IH 增强学习和记忆受损易感性的主要途径。