Journal article
Prolonged exposure to NMDAR antagonist induces cell-type specific changes of glutamatergic receptors in rat prefrontal cortex
Neuropharmacology, v 62(4), pp 1808-1822
Mar 2012
PMID: 22182778
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 α-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.
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Details
- Title
- Prolonged exposure to NMDAR antagonist induces cell-type specific changes of glutamatergic receptors in rat prefrontal cortex
- Creators
- Huai-Xing Wang - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USAWen-Jun Gao
- Publication Details
- Neuropharmacology, v 62(4), pp 1808-1822
- Publisher
- Elsevier; England
- Grant note
- R01 MH085666 / NIMH NIH HHS R01 MH085666-03 / NIMH NIH HHS R21 MH232307 / NIMH NIH HHS R01 MH085666-04 / NIMH NIH HHS R01 MH085666-02 / NIMH NIH HHS R01 MH232395 / NIMH NIH HHS R01 MH085666-01A1 / NIMH NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000301221500022
- Scopus ID
- 2-s2.0-84856443222
- Other Identifier
- 991014878024604721
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- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy