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

Neuropsychopharmacology. 2009 Jul;34(8):2028-40. doi: 10.1038/npp.2009.20. Epub 2009 Feb 25.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Aging / metabolism
  • Animals
  • Animals, Newborn
  • Cell Differentiation / physiology*
  • Cell Shape / physiology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Epigenesis, Genetic / physiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Interneurons / cytology
  • Interneurons / drug effects
  • Interneurons / metabolism*
  • Lysine / analogs & derivatives
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / growth & development*
  • Prefrontal Cortex / metabolism*
  • Rats
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Schizophrenia / etiology
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology
  • Staining and Labeling
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • biocytin
  • Lysine