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PMID:12761821

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Citation

Moga, DE, Janssen, WG, Vissavajjhala, P, Czelusniak, SM, Moran, TM, Hof, PR and Morrison, JH (2003) Glutamate receptor subunit 3 (GluR3) immunoreactivity delineates a subpopulation of parvalbumin-containing interneurons in the rat hippocampus. J. Comp. Neurol. 462:15-28

Abstract

Rasmussen's encephalitis is a childhood disease resulting in intractable seizures associated with hippocampal and neocortical inflammation. An autoantibody against the GluR3 subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors is implicated in the pathophysiology of Rasmussen's encephalitis. AMPA receptors mediate excitatory neurotransmission in the brain and contain combinations of four subunits (GluR1-4). Although the distributions of GluR1, GluR2, and GluR4 are known in some detail, the cellular distribution of GluR3 in the mammalian brain remains to be described. We developed and characterized a GluR3-specific monoclonal antibody and quantified the cellular distribution of GluR3 in CA1 of the rat hippocampus. GluR3 immunoreactivity was detected in all pyramidal neurons and astrocytes and in most interneurons. We quantified the intensity of GluR3 immunoreactivity in interneuron subtypes defined by their calcium-binding protein content. GluR3 immunofluorescence, but not GluR1 or GluR2 immunofluorescence, was significantly elevated in somata of parvalbumin-containing interneurons compared to pyramidal somata. Strikingly, increased GluR3 immunofluorescence was not observed in calbindin- and calretinin-containing interneurons. Furthermore, 24% of parvalbumin-containing interneurons could be distinguished from surrounding neurons based on their intense GluR3 immunoreactivity. This subpopulation had significantly elevated GluR3 immunoreactivity compared to the rest of parvalbumin-containing interneurons. Electron microscopy revealed enriched GluR3 immunoreactivity in parvalbumin-containing perikarya at cytoplasmic and postsynaptic sites. Parvalbumin-containing interneurons, potent inhibitors of cortical pyramidal neurons, are vulnerable in the brains of epileptic patients. Our findings suggest that the somata of these interneurons are enriched in GluR3, which may render them vulnerable to pathological states such as epilepsy and Rasmussen's encephalitis.

Links

PubMed Online version:10.1002/cne.10710

Keywords

Animals; Autoantibodies/immunology; Calbindin 2; Calbindins; Encephalitis/immunology; Encephalitis/metabolism; Encephalitis/physiopathology; Hippocampus/metabolism; Hippocampus/ultrastructure; Immunohistochemistry; Interneurons/metabolism; Interneurons/ultrastructure; Male; Mice; Mice, Inbred BALB C; Microscopy, Electron; Neural Inhibition/physiology; Neural Pathways/metabolism; Neural Pathways/ultrastructure; Parvalbumins/metabolism; Pyramidal Cells/metabolism; Pyramidal Cells/ultrastructure; Rats; Rats, Sprague-Dawley/anatomy & histology; Rats, Sprague-Dawley/metabolism; Receptors, AMPA/metabolism; S100 Calcium Binding Protein G/metabolism; Synapses/metabolism; Synapses/ultrastructure; Up-Regulation/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:GRIA3

located_in

GO:0099061: integral component of postsynaptic density membrane

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:GRIA3

located_in

GO:0098978: glutamatergic synapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:GRIA3

part_of

GO:0099061: integral component of postsynaptic density membrane

ECO:0006003: electron microscopy evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:GRIA3

part_of

GO:0098978: glutamatergic synapse

ECO:0006003: electron microscopy evidence used in manual assertion

C

part_of:(UBERON:0002421)

Seeded From UniProt

complete

Notes

See also

References

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