Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
Department of Surgery B- HaEmek Medical Center, Faculty of Medicine, Technion: Israel Institute of Technology, Afula Israel.
Neurobiol Learn Mem. 2018 Oct;154:5-11. doi: 10.1016/j.nlm.2018.02.011. Epub 2018 Feb 10.
Metaplasticity is the dynamic regulation of the ability to induce activity-dependent synaptic plasticity and is governed by the prior history of the synapses. Previous reports by others and us have shown that behavioral stress induces a form of emotional metaplasticity that affects the ability to induce LTP in the subiculum-medial prefrontal cortex pathway, which depends on NMDA receptors (NMDAr). However, studies addressing the effects of stress on LTP and metaplasticity have mainly focused on the adult animal. Here we compared the effects of exposure to stress on the induction of LTP in adult and juvenile animals and examined whether a low dose of NMDAr antagonist (MK801) that does not affect LTP per se would differentially affect stress-induced metaplasticity in adult and juvenile animals. Our findings show that exposure to the elevated platform differentially affects the induction of LTP in adult and juvenile animals. Specifically, whereas exposure to stress resulted in impaired LTP in adult animals, it resulted in enhanced LTP in juvenile animals. Similarly, while MK801 failed to inhibit the induction of LTP in both age groups, it resulted in inhibition of stress-induced enhanced LTP in juvenile animals, but did not affect stress-induced impaired LTP in adult animals. Taken together, these findings demonstrate that emotional metaplasticity is differently dependent on NMDAr in adult and juvenile animals that may stem from developmental differences in the NMDA receptor representation. These results further confirm that the mechanisms of plasticity following stress are distinctive in the two groups of age.
易化现象是指诱导活性依赖突触可塑性的能力的动态调节，受突触先前历史的控制。之前其他人的报告和我们的研究表明，行为应激诱导一种情绪易化现象，影响内侧前额叶皮层-海马体通路中 LTP 的诱导能力，这依赖于 NMDA 受体（NMDAr）。然而，研究应激对 LTP 和易化现象的影响主要集中在成年动物上。在这里，我们比较了应激对成年和幼年动物 LTP 诱导的影响，并研究了低剂量的 NMDA 受体拮抗剂（MK801）是否会对成年和幼年动物的应激诱导易化现象产生不同的影响，而这种剂量本身不会影响 LTP。我们的研究结果表明，暴露在高架平台上会对成年和幼年动物的 LTP 诱导产生不同的影响。具体来说，虽然应激暴露导致成年动物的 LTP 受损，但它导致幼年动物的 LTP 增强。同样，虽然 MK801 不能抑制两个年龄组 LTP 的诱导，但它抑制了幼年动物应激诱导的增强 LTP，但不影响成年动物应激诱导的受损 LTP。总之，这些发现表明，情绪易化现象在成年和幼年动物中对 NMDA 受体的依赖性不同，这可能源于 NMDA 受体表达在发育上的差异。这些结果进一步证实，应激后可塑性的机制在这两个年龄组中是不同的。
