A translational EEG-based approach to assess modulation of long-lasting NMDAR-dependent synaptic plasticity
A translational EEG-based approach to assess modulation of long-lasting NMDAR-dependent synaptic plasticity
复制标题
DOI：
10.1007/s00213-019-05341-w
复制
发表时间：
2019-12-01
影响因子：
3.4
通讯作者：
Moskal, J. R.
中科院分区：
文献类型：
--
作者：
Burgdorf, Jeffrey S.;Christian, E. P.;Moskal, J. R.
研究背景NYX-2925是一种新型的N-甲基-D-天冬氨酸受体（NMDAR）调节剂，在体外可促进NMDAR依赖的长时程增强（LTP）和在体学习记忆。结果NYX-2925（1、10 mg/kg）可增加听觉强直后1h aLTP，aLTP由强直后140-180 ms的aLTP减去强直前差值波形测得。NYX-2925（0.1、1 mg/kg PO）促进通过差波形（即，偏差音减去标准音）。NYX-2925（0.1、1、10 mg/kg PO）也增强了静息态α qEEG功率。相反，NMDAR谷氨酸盐位点拮抗剂CPP（10 mg/kg IP）降低α功率和MMN，并产生与NYX-2925对aLTP.Conclusions相反的效果，这些数据表明，NYX-2925激活NMDAR增强体内突触可塑性，这可能既减少神经系统疾病的症状，又可作为药物作用的生物标志物。这是第一次证明了一个持久的（1小时后破伤风）的影响，NMDAR调制突触可塑性过程中，在体内使用非侵入性技术在自由行为的动物。
Background NYX-2925 is a novel N-methyl-D-aspartate receptor (NMDAR) modulator that has been shown to facilitate both NMDAR-dependent long-term potentiation (LTP) in vitro and learning and memory in vivo.Objective The present studies examine the effects of NYX-2925 on NMDAR-dependent auditory LTP (aLTP) in vivo.Methods NMDAR-dependent aLTP and NMDAR-dependent auditory mismatch negativity (MMN) was measured, as well as changes in resting-state qEEG power.Results NYX-2925 (1, 10 mg/kg PO) increased aLTP 1 h after auditory tetanus measured by the post-minus pre-tetanus difference waveform 140-180 ms post tone onset. NYX-2925 (0.1, 1 mg/kg PO) facilitated MMN measured by the difference waveform (i.e., deviant minus standard tones). NYX-2925 (0.1, 1, 10 mg/kg PO) also enhanced resting-state alpha qEEG power. Conversely, the NMDAR glutamate site antagonist CPP (10 mg/kg IP) reduces alpha power and MMN and produces an opposite effect as NYX-2925 on aLTP.Conclusions Together, these data suggest that the activation of the NMDAR by NYX-2925 enhances synaptic plasticity in vivo, which may both reduce symptoms of neurological disorders and serve as a biomarker for drug effects. This is the first demonstration of a long-lasting (1-h post-tetanus) effect of NMDAR modulation on synaptic plasticity processes in vivo using a noninvasive technique in freely behaving animals.