Vasuta Cristina, Caunt Charlotte, James Rachel, Samadi Shervin, Schibuk Elizabeth, Kannangara Timal, Titterness Andrea K, Christie Brian R
The Neuroscience Program, University of British Columbia, Vancouver, British Columbia, Canada.
Hippocampus. 2007;17(12):1201-8. doi: 10.1002/hipo.20349.
We examined synaptic plasticity in the dentate gyrus (DG) of the hippocampus in vitro in juvenile C57Bl6 mice (28-40 days of age), housed in control conditions with minimal enrichment (Controls) or with access to an exercise wheel (Runners). LTP expression was significantly greater in slices from Runners than in those from Controls, but could be blocked by APV in both groups. LTP was significantly reduced by NR2B subunit antagonists in both groups. NVP-AAM077, an antagonist with a higher preference for NR2A subunits over NR2B subunits, blocked LTP in slices from Runners and produced a slight depression in Control animals. LTD in the DG was also blocked by APV, but not by either of the NR2B specific antagonists. Strikingly, NVP-AAM077 prevented LTD in Runners, but not in Control animals, suggesting an increased involvement of NR2A subunits in LTD in animals that exercise. NVP-AAM077 did not block LTD in NR2A Knock Out (KO) animals that exercised, as expected. In an attempt to discern whether NMDA receptors located at extrasynaptic sites could play a role in the induction of LTD, DL-TBOA was used to block excitatory amino acid transport and increase extracellular glutamate levels. Under these conditions, LTD was not blocked by the co-application of a specific NR2B subunit antagonist in either group, but NVP-AAM077 again blocked LTD selectively in Runners. These results indicate that NR2A and NR2B subunits play a significant role in LTP in the DG, and that exercise can significantly alter the contribution of NMDA NR2A subunits to LTD.
我们在体外检测了幼年C57Bl6小鼠（28 - 40日龄）海马齿状回（DG）的突触可塑性。这些小鼠饲养在控制条件下，富集程度最低（对照组）或可使用运动轮（跑步组）。跑步组切片中的长时程增强（LTP）表达显著高于对照组，但两组的LTP均可被APV阻断。两组中NR2B亚基拮抗剂均显著降低了LTP。NVP - AAM077是一种对NR2A亚基的偏好高于NR2B亚基的拮抗剂，它阻断了跑步组切片中的LTP，并在对照组动物中产生了轻微的抑制作用。DG中的长时程抑制（LTD）也被APV阻断，但未被任何一种NR2B特异性拮抗剂阻断。令人惊讶的是，NVP - AAM077阻止了跑步组动物的LTD，但未阻止对照组动物的LTD，这表明在运动的动物中，NR2A亚基在LTD中的参与度增加。正如预期的那样，NVP - AAM077并未阻断运动的NR2A基因敲除（KO）动物中的LTD。为了探究位于突触外位点的N - 甲基 - D - 天冬氨酸（NMDA）受体是否可能在LTD的诱导中发挥作用，使用了DL - TBOA来阻断兴奋性氨基酸转运并提高细胞外谷氨酸水平。在这些条件下，两组中特异性NR2B亚基拮抗剂的共同应用均未阻断LTD，但NVP - AAM077再次选择性地阻断了跑步组动物的LTD。这些结果表明，NR2A和NR2B亚基在DG的LTP中发挥重要作用，并且运动可以显著改变NMDA NR2A亚基对LTD的贡献。
