Prolonged exposure to NMDAR antagonist induces cell-type specific changes of glutamatergic receptors in rat prefrontal cortex

NEUROPHARMACOLOGY

卷:62

Article

Wang, Huai-Xing¹  Gao, Wen-Jun¹ 

[1] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA

关键词: MK-801;    AMPA receptors;    Fast-spiking interneurons;    NMDA receptor hypofunction;    Schizophrenia;   

DOI  :  10.1016/j.neuropharm.2011.11.024

来源: Elsevier

【 摘 要 】

N-methyl-D-aspartic acid (NMDA) receptors are critical for both normal brain functions and the pathogenesis of schizophrenia. We investigated the functional changes of glutamatergic receptors in the pyramidal cells and fast-spiking (FS) interneurons in the adolescent rat prefrontal cortex in MK-801 model of schizophrenia. We found that although both pyramidal cells and FS interneurons were affected by in vivo subchronic blockade of NMDA receptors, MK-801 induced distinct changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in the FS interneurons compared with pyramidal cells. Specifically, the amplitude, but not the frequency, of AMPA-mediated miniature excitatory postsynaptic currents (mEPSCs) in FS interneurons was significantly decreased whereas both the frequency and amplitude in pyramidal neurons were increased. In addition, MK-801-induced new presynaptic NMDA receptors were detected in the glutamatergic terminals targeting pyramidal neurons but not FS interneurons. MK-801 also induced distinct alterations in FS interneurons but not in pyramidal neurons, including significantly decreased rectification index and increased calcium permeability. These data suggest a distinct cell-type specific and homeostatic synaptic scaling and redistribution of AMPA and NMDA receptors in response to the subchronic blockade of NMDA receptors and thus provide a direct mechanistic explanation for the NMDA hypofunction hypothesis that have long been proposed for the schizophrenia pathophysiology. (c) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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