Abstract
N-methyl-D-aspartate (NMDA) receptors play crucial roles in glutamate-mediated synaptic transmission and plasticity and are involved in a variety of brain functions. Specific single nucleotide polymorphisms (SNPs) in the genes encoding NMDA receptor subunits have been associated with some neuropsychiatric disorders involving altered glutamate transmission, but how these polymorphisms impact on synaptic function in humans is unknown. Here, the role of NMDA receptors in the control of cortical excitability and plasticity was explored by comparing the response to single, paired, and repetitive transcranial magnetic stimulations of the motor cortex in 77 healthy subjects carrying specific allelic variants of the NR1 subunit gene (GRIN1 rs4880213 and rs6293) or of the NR2B subunit gene (GRIN2B rs7301328, rs3764028, and rs1805247). Our results showed that individuals homozygous for the T allele in the rs4880213 GRIN1 SNP had reduced intracortical inhibition, as expected for enhanced glutamatergic excitation in these subjects. Furthermore, individuals carrying the G allele in the rs1805247 GRIN2B SNP show greater intracortical facilitation and greater long-term potentiation-like cortical plasticity after intermittent θ-burst stimulation. Our results provide novel insights into the function of NMDA receptors in the human brain and might contribute to the clarification of the synaptic bases of severe neuropsychiatric disorders associated with defective glutamate transmission.
| Original language | English |
|---|---|
| Pages (from-to) | 1637-1643 |
| Number of pages | 7 |
| Journal | Journal of Neurophysiology |
| Volume | 106 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Oct 2011 |
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Keywords
- Glutamate
- Synaptic plasticity
- Transcranial magnetic stimulation
ASJC Scopus subject areas
- Physiology
- Neuroscience(all)
Cite this
Genetic variants of the NMDA receptor influence cortical excitability and plasticity in humans. / Mori, Francesco; Ribolsi, Michele; Kusayanagi, Hajime; Siracusano, Alberto; Mantovani, Vilma; Marasco, Elena; Bernardi, Giorgio; Centonze, Diego.
In: Journal of Neurophysiology, Vol. 106, No. 4, 10.2011, p. 1637-1643.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic variants of the NMDA receptor influence cortical excitability and plasticity in humans
AU - Mori, Francesco
AU - Ribolsi, Michele
AU - Kusayanagi, Hajime
AU - Siracusano, Alberto
AU - Mantovani, Vilma
AU - Marasco, Elena
AU - Bernardi, Giorgio
AU - Centonze, Diego
PY - 2011/10
Y1 - 2011/10
N2 - N-methyl-D-aspartate (NMDA) receptors play crucial roles in glutamate-mediated synaptic transmission and plasticity and are involved in a variety of brain functions. Specific single nucleotide polymorphisms (SNPs) in the genes encoding NMDA receptor subunits have been associated with some neuropsychiatric disorders involving altered glutamate transmission, but how these polymorphisms impact on synaptic function in humans is unknown. Here, the role of NMDA receptors in the control of cortical excitability and plasticity was explored by comparing the response to single, paired, and repetitive transcranial magnetic stimulations of the motor cortex in 77 healthy subjects carrying specific allelic variants of the NR1 subunit gene (GRIN1 rs4880213 and rs6293) or of the NR2B subunit gene (GRIN2B rs7301328, rs3764028, and rs1805247). Our results showed that individuals homozygous for the T allele in the rs4880213 GRIN1 SNP had reduced intracortical inhibition, as expected for enhanced glutamatergic excitation in these subjects. Furthermore, individuals carrying the G allele in the rs1805247 GRIN2B SNP show greater intracortical facilitation and greater long-term potentiation-like cortical plasticity after intermittent θ-burst stimulation. Our results provide novel insights into the function of NMDA receptors in the human brain and might contribute to the clarification of the synaptic bases of severe neuropsychiatric disorders associated with defective glutamate transmission.
AB - N-methyl-D-aspartate (NMDA) receptors play crucial roles in glutamate-mediated synaptic transmission and plasticity and are involved in a variety of brain functions. Specific single nucleotide polymorphisms (SNPs) in the genes encoding NMDA receptor subunits have been associated with some neuropsychiatric disorders involving altered glutamate transmission, but how these polymorphisms impact on synaptic function in humans is unknown. Here, the role of NMDA receptors in the control of cortical excitability and plasticity was explored by comparing the response to single, paired, and repetitive transcranial magnetic stimulations of the motor cortex in 77 healthy subjects carrying specific allelic variants of the NR1 subunit gene (GRIN1 rs4880213 and rs6293) or of the NR2B subunit gene (GRIN2B rs7301328, rs3764028, and rs1805247). Our results showed that individuals homozygous for the T allele in the rs4880213 GRIN1 SNP had reduced intracortical inhibition, as expected for enhanced glutamatergic excitation in these subjects. Furthermore, individuals carrying the G allele in the rs1805247 GRIN2B SNP show greater intracortical facilitation and greater long-term potentiation-like cortical plasticity after intermittent θ-burst stimulation. Our results provide novel insights into the function of NMDA receptors in the human brain and might contribute to the clarification of the synaptic bases of severe neuropsychiatric disorders associated with defective glutamate transmission.
KW - Glutamate
KW - Synaptic plasticity
KW - Transcranial magnetic stimulation
UR - http://www.scopus.com/inward/record.url?scp=80054032039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054032039&partnerID=8YFLogxK
U2 - 10.1152/jn.00318.2011
DO - 10.1152/jn.00318.2011
M3 - Article
C2 - 21753020
AN - SCOPUS:80054032039
VL - 106
SP - 1637
EP - 1643
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
SN - 0022-3077
IS - 4
ER -