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Cell type-specific development of NMDA receptors in the interneurons of rat prefrontal cortex
Journal article   Open access   Peer reviewed

Cell type-specific development of NMDA receptors in the interneurons of rat prefrontal cortex

Huai-Xing Wang and Wen-Jun Gao
Neuropsychopharmacology (New York, N.Y.), v 34(8), pp 2028-2040
Jul 2009
DOI: https://doi.org/10.1038/npp.2009.20
PMID: 19242405
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1038/npp.2009.20View
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Abstract

Schizophrenia - metabolism Synaptic Transmission - physiology Receptors, N-Methyl-D-Aspartate - metabolism Dendrites - ultrastructure Prefrontal Cortex - growth & development Epigenesis, Genetic - physiology Schizophrenia - physiopathology Synaptic Transmission - drug effects Interneurons - cytology Cell Differentiation - physiology Action Potentials - drug effects Organ Culture Techniques Receptors, AMPA - metabolism Animals, Newborn Dendrites - drug effects Dendrites - metabolism Lysine - analogs & derivatives Receptors, N-Methyl-D-Aspartate - drug effects Interneurons - drug effects Rats Excitatory Amino Acid Antagonists - pharmacology Prefrontal Cortex - cytology GABA Antagonists - pharmacology Schizophrenia - etiology Action Potentials - physiology Patch-Clamp Techniques Animals Interneurons - metabolism Staining and Labeling Prefrontal Cortex - metabolism Glutamic Acid - metabolism Cell Shape - physiology Aging - metabolism
In the prefrontal cortex, N-methyl-D-aspartic acid (NMDA) receptors (NMDARs) are critical not only for normal prefrontal functions but also for the pathological processes of schizophrenia. Little is known, however, about the developmental properties of NMDARs in the functionally diverse sub-populations of interneurons. We investigated the developmental changes of NMDARs in rat prefrontal interneurons using patch clamp recording in cortical slices. We found that fast-spiking (FS) interneurons exhibited properties of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA currents distinct from those in regular spiking (RS) and low-threshold spiking (LTS) interneurons, particularly during the adolescent period. In juvenile animals, most (73%) of the FS cells demonstrated both AMPA and NMDA currents. The NMDA currents, however, gradually became undetectable during cortical development, with most (74%) of the FS cells exhibiting no NMDA current in adults. In contrast, AMPA and NMDA currents in RS and LTS interneurons were relatively stable, without significant changes from juveniles to adults. Moreover, even in FS cells with NMDA currents, the NMDA/AMPA ratio dramatically decreased during the adolescent period but returned to juvenile level in adults, compared with the relatively stable ratios in RS and LTS interneurons. These data suggest that FS interneurons in the prefrontal cortex undergo dramatic changes in glutamatergic receptors during the adolescent period. These properties may make FS cells particularly sensitive and vulnerable to epigenetic stimulation, thus contributing to the onset of many psychiatric disorders, including schizophrenia.

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Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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