Genetic variations of the NR3A subunit of the NMDA receptor modulate prefrontal cerebral activity in humans.
BACKGROUND
Recently, a novel N-methyl-D-aspartate (NMDA) receptor subunit, NR3A, has been discovered in the brain. This subunit decreases NMDA receptor activity by modulating the calcium permeability of the receptor channel and current density in cortical cells. Because the NR3A is expressed in the human prefrontal cortex, we hypothesized that genetic variations of the NR3A subunit modulate prefrontal activation.


METHODS
Electromagnetic activity during selective attention (auditory oddball task with target processing) was measured in 281 healthy subjects. Genotyping of a missense variation (rs10989591, Val362Met) of the NR3A gene was performed.


RESULTS
Individuals carrying Val/Val genotype showed significantly reduced frontal P300 amplitudes compared with Met/Met subjects. Subsequent low-resolution electromagnetic source analysis revealed that this group difference is likely caused by reduced activation in the inferior frontal gyrus.


CONCLUSIONS
It was shown for the first time that the genetic constitution of the subunit composition of NMDA receptor regulation might be relevant for prefrontal information processing in humans. The results underline the pivotal role of glutamate in frontal lobe function and indicate that the NR3A subunit could be a plausible candidate gene for diseases with prefrontal dysfunctions.
Gallinat
Jürgen
J
Klinik für Psychiatrie and Psychotherapie, Charité Universitätsmedizin, Berlin. juergen.gallinat@charite.de
Götz
Thomas
T
Kalus
Peter
P
Bajbouj
Malek
M
Sander
Thomas
T
Winterer
Georg
G
D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000502:physiology*; D001931:Brain Mapping; D004569:Electroencephalography / Q000379:methods; D018913:Event-Related Potentials, P300 / Q000235:genetics* / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000502:physiology; D014633:Valine / Q000235:genetics
C464437:NR3A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D008715:Methionine; D014633:Valine