Glutamate receptor subunit 3 (GLuR3) immunoreactivity delineates a subpopulation of parvalbumin-containing interneurons in the rat hippocampus

Diana E. Moga, Willlam G.M. Janssen, Prabhakar Vissavajjhala, Sharon M. Czelusniak, Thomas M. Moran, Patrick R. Hof, John Morrison

Research output: Contribution to journalArticle

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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 a-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 immuno-fluorescence 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.

Original languageEnglish (US)
Pages (from-to)15-28
Number of pages14
JournalJournal of Comparative Neurology
Volume462
Issue number1
DOIs
StatePublished - Jul 14 2003
Externally publishedYes

Fingerprint

Parvalbumins
Interneurons
Hippocampus
Carisoprodol
Encephalitis
AMPA Receptors
Pyramidal Cells
Fluorescent Antibody Technique
Brain
Isoxazoles
Calbindin 2
Calbindins
Calcium-Binding Proteins
AMPA 3 glutamate receptor ionotropic
Synaptic Transmission
Astrocytes
Autoantibodies
Epilepsy
Electron Microscopy
Seizures

Keywords

  • AMPA receptors
  • Epilepsy
  • Excitatory amino acids
  • Rasmussen's encephalitis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Glutamate receptor subunit 3 (GLuR3) immunoreactivity delineates a subpopulation of parvalbumin-containing interneurons in the rat hippocampus. / Moga, Diana E.; Janssen, Willlam G.M.; Vissavajjhala, Prabhakar; Czelusniak, Sharon M.; Moran, Thomas M.; Hof, Patrick R.; Morrison, John.

In: Journal of Comparative Neurology, Vol. 462, No. 1, 14.07.2003, p. 15-28.

Research output: Contribution to journalArticle

Moga, Diana E. ; Janssen, Willlam G.M. ; Vissavajjhala, Prabhakar ; Czelusniak, Sharon M. ; Moran, Thomas M. ; Hof, Patrick R. ; Morrison, John. / Glutamate receptor subunit 3 (GLuR3) immunoreactivity delineates a subpopulation of parvalbumin-containing interneurons in the rat hippocampus. In: Journal of Comparative Neurology. 2003 ; Vol. 462, No. 1. pp. 15-28.
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AU - Vissavajjhala, Prabhakar

AU - Czelusniak, Sharon M.

AU - Moran, Thomas M.

AU - Hof, Patrick R.

AU - Morrison, John

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AB - Rasmussen's encephalitis is a childhood disease resulting in intractable seizures associated with hippocampal and neocortical inflammation. An autoantibody against the GluR3 subunit of a-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 immuno-fluorescence 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.

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