Shojaei Amir, Anaraki Afsaneh Kamali, Mirnajafi-Zadeh Javad, Atapour Nafiseh
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran; Neuroscience Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia.
Int J Dev Neurosci. 2017 Apr;57:56-61. doi: 10.1016/j.ijdevneu.2017.01.006. Epub 2017 Jan 15.
Early enriched environment (EE) prevents several deficits associated with postnatal MK-801 [N-Methyl-d-Aspartate (NMDA) receptor antagonist] treatment such as cognitive and locomotor deficits. We sought physiological correlates to such changes by looking at inhibitory synaptic inputs onto pyramidal cells in a prefrontal cortex slice preparation. Pharmacologically isolated γ-amino-butyric acid (GABA) receptor-mediated currents were measured using whole-cell patch clamp recordings. Wistar rats were raised in standard or EE from birth up to the time of experiments and were injected with saline or MK-801 (1mg/kg) on postnatal days (P) 6-10. We recorded miniature inhibitory post-synaptic currents (mIPSCs) of pyramidal cells in layer II/III of prefrontal cortex and measured their frequency, amplitude and kinetics. In control animals, the amplitude and frequency of mIPSCs increased strikingly during development from P21 to P28. MK-801 accelerated the development of mIPSCs frequency but caused a significant decrease in the amplitude of mIPSCs on P28 suggesting a significant reduction of inhibition onto pyramidal cells. EE per se led to a significant increase in both frequency and amplitude of mIPSCs, but its application to MK-801-treated rats resulted in moderate rescue of GABAergic transmission on P28. We conclude that postnatal MK-801 leads to reduced inhibitory transmission onto pyramidal cells of prefrontal cortex at adolescence which may underlie behavioural and morphological differences detected in vivo in rats. EE presentation from birth rather prevents GABAergic alterations associated with postnatal MK-801 treatment at adolescence.
早期丰富环境（EE）可预防与出生后给予MK-801 [N-甲基-D-天冬氨酸（NMDA）受体拮抗剂]治疗相关的多种缺陷，如认知和运动缺陷。我们通过观察前额叶皮层脑片制备中锥体细胞上的抑制性突触输入，来寻找这些变化的生理相关性。使用全细胞膜片钳记录法测量药理学分离的γ-氨基丁酸（GABA）受体介导的电流。Wistar大鼠从出生到实验时饲养在标准环境或丰富环境中，并在出生后第6至10天注射生理盐水或MK-801（1mg/kg）。我们记录了前额叶皮层第II/III层锥体细胞的微小抑制性突触后电流（mIPSCs），并测量了它们的频率、幅度和动力学。在对照动物中，从出生后第21天到第28天，mIPSCs的幅度和频率在发育过程中显著增加。MK-801加速了mIPSCs频率的发育，但导致出生后第28天mIPSCs的幅度显著降低，表明对锥体细胞的抑制作用显著减弱。丰富环境本身导致mIPSCs的频率和幅度均显著增加，但其应用于MK-801处理的大鼠可在出生后第
