Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones

F. Suárez, Q. Zhao, Daniel T Monaghan, D. E. Jane, S. Jones, A. J. Gibb

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The nigra substantia nigra pars compacta (SNc) and substantia pars reticulata (SNr) form two major basal ganglia components with different functional roles. SNc dopaminergic (DA) neurones are vulnerable to cell death in Parkinson's disease, and NMDA receptor activation is a potential contributing mechanism. We have investigated the sensitivity of whole-cell and synaptic NMDA responses to intracellular ATP and GTP application in the SNc and SNr from rats on postnatal day (P) 7 and P28. Both NMDA current density (pA/pF) and desensitization to prolonged or repeated NMDA application were greater in the SNr than in the SNc. When ATP levels were not supplemented, responses to prolonged NMDA administration desensitized in P7 SNc DA neurones but not at P28. At P28, SNr neurones desensitized more than SNc neurones, with or without added ATP. Responses to brief NMDA applications and synaptic NMDA currents were not sensitive to inclusion of ATP in the pipette solution. To investigate these differences between the SNc and SNr, NR2 subunit-selective antagonists were tested. NMDA currents were inhibited by ifenprodil (10 μm) and UBP141 (4 μm), but not by Zn 2+ (100 nm), in both the SNr and SNc, suggesting that SNc and SNr neurones express similar receptor subunits; NR2B and NR2D, but not NR2A. The different NMDA response properties in the SNc and SNr may be caused by differences in receptor modulation and/or trafficking. The vulnerability of SNc DA neurones to cell death is not correlated with NMDA current density or receptor subtypes, but could in part be related to inadequate NMDA receptor desensitization.

Original languageEnglish (US)
Pages (from-to)359-367
Number of pages9
JournalEuropean Journal of Neuroscience
Volume32
Issue number3
DOIs
StatePublished - Aug 1 2010

Fingerprint

N-Methyl-D-Aspartate Receptors
N-Methylaspartate
Neurons
Dopaminergic Neurons
Adenosine Triphosphate
Pars Reticulata
Pars Compacta
Cell Death
Guanosine Triphosphate
Basal Ganglia
Parkinson Disease

Keywords

  • Parkinson's disease
  • excitotoxicity
  • glutamate receptor
  • ifenprodil
  • triheteromeric

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones. / Suárez, F.; Zhao, Q.; Monaghan, Daniel T; Jane, D. E.; Jones, S.; Gibb, A. J.

In: European Journal of Neuroscience, Vol. 32, No. 3, 01.08.2010, p. 359-367.

Research output: Contribution to journalArticle

Suárez, F. ; Zhao, Q. ; Monaghan, Daniel T ; Jane, D. E. ; Jones, S. ; Gibb, A. J. / Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones. In: European Journal of Neuroscience. 2010 ; Vol. 32, No. 3. pp. 359-367.
@article{2c1fdd91ba01420fbde42f4039bfaccd,
title = "Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones",
abstract = "The nigra substantia nigra pars compacta (SNc) and substantia pars reticulata (SNr) form two major basal ganglia components with different functional roles. SNc dopaminergic (DA) neurones are vulnerable to cell death in Parkinson's disease, and NMDA receptor activation is a potential contributing mechanism. We have investigated the sensitivity of whole-cell and synaptic NMDA responses to intracellular ATP and GTP application in the SNc and SNr from rats on postnatal day (P) 7 and P28. Both NMDA current density (pA/pF) and desensitization to prolonged or repeated NMDA application were greater in the SNr than in the SNc. When ATP levels were not supplemented, responses to prolonged NMDA administration desensitized in P7 SNc DA neurones but not at P28. At P28, SNr neurones desensitized more than SNc neurones, with or without added ATP. Responses to brief NMDA applications and synaptic NMDA currents were not sensitive to inclusion of ATP in the pipette solution. To investigate these differences between the SNc and SNr, NR2 subunit-selective antagonists were tested. NMDA currents were inhibited by ifenprodil (10 μm) and UBP141 (4 μm), but not by Zn 2+ (100 nm), in both the SNr and SNc, suggesting that SNc and SNr neurones express similar receptor subunits; NR2B and NR2D, but not NR2A. The different NMDA response properties in the SNc and SNr may be caused by differences in receptor modulation and/or trafficking. The vulnerability of SNc DA neurones to cell death is not correlated with NMDA current density or receptor subtypes, but could in part be related to inadequate NMDA receptor desensitization.",
keywords = "Parkinson's disease, excitotoxicity, glutamate receptor, ifenprodil, triheteromeric",
author = "F. Su{\'a}rez and Q. Zhao and Monaghan, {Daniel T} and Jane, {D. E.} and S. Jones and Gibb, {A. J.}",
year = "2010",
month = "8",
day = "1",
doi = "10.1111/j.1460-9568.2010.07298.x",
language = "English (US)",
volume = "32",
pages = "359--367",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones

AU - Suárez, F.

AU - Zhao, Q.

AU - Monaghan, Daniel T

AU - Jane, D. E.

AU - Jones, S.

AU - Gibb, A. J.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - The nigra substantia nigra pars compacta (SNc) and substantia pars reticulata (SNr) form two major basal ganglia components with different functional roles. SNc dopaminergic (DA) neurones are vulnerable to cell death in Parkinson's disease, and NMDA receptor activation is a potential contributing mechanism. We have investigated the sensitivity of whole-cell and synaptic NMDA responses to intracellular ATP and GTP application in the SNc and SNr from rats on postnatal day (P) 7 and P28. Both NMDA current density (pA/pF) and desensitization to prolonged or repeated NMDA application were greater in the SNr than in the SNc. When ATP levels were not supplemented, responses to prolonged NMDA administration desensitized in P7 SNc DA neurones but not at P28. At P28, SNr neurones desensitized more than SNc neurones, with or without added ATP. Responses to brief NMDA applications and synaptic NMDA currents were not sensitive to inclusion of ATP in the pipette solution. To investigate these differences between the SNc and SNr, NR2 subunit-selective antagonists were tested. NMDA currents were inhibited by ifenprodil (10 μm) and UBP141 (4 μm), but not by Zn 2+ (100 nm), in both the SNr and SNc, suggesting that SNc and SNr neurones express similar receptor subunits; NR2B and NR2D, but not NR2A. The different NMDA response properties in the SNc and SNr may be caused by differences in receptor modulation and/or trafficking. The vulnerability of SNc DA neurones to cell death is not correlated with NMDA current density or receptor subtypes, but could in part be related to inadequate NMDA receptor desensitization.

AB - The nigra substantia nigra pars compacta (SNc) and substantia pars reticulata (SNr) form two major basal ganglia components with different functional roles. SNc dopaminergic (DA) neurones are vulnerable to cell death in Parkinson's disease, and NMDA receptor activation is a potential contributing mechanism. We have investigated the sensitivity of whole-cell and synaptic NMDA responses to intracellular ATP and GTP application in the SNc and SNr from rats on postnatal day (P) 7 and P28. Both NMDA current density (pA/pF) and desensitization to prolonged or repeated NMDA application were greater in the SNr than in the SNc. When ATP levels were not supplemented, responses to prolonged NMDA administration desensitized in P7 SNc DA neurones but not at P28. At P28, SNr neurones desensitized more than SNc neurones, with or without added ATP. Responses to brief NMDA applications and synaptic NMDA currents were not sensitive to inclusion of ATP in the pipette solution. To investigate these differences between the SNc and SNr, NR2 subunit-selective antagonists were tested. NMDA currents were inhibited by ifenprodil (10 μm) and UBP141 (4 μm), but not by Zn 2+ (100 nm), in both the SNr and SNc, suggesting that SNc and SNr neurones express similar receptor subunits; NR2B and NR2D, but not NR2A. The different NMDA response properties in the SNc and SNr may be caused by differences in receptor modulation and/or trafficking. The vulnerability of SNc DA neurones to cell death is not correlated with NMDA current density or receptor subtypes, but could in part be related to inadequate NMDA receptor desensitization.

KW - Parkinson's disease

KW - excitotoxicity

KW - glutamate receptor

KW - ifenprodil

KW - triheteromeric

UR - http://www.scopus.com/inward/record.url?scp=77955129538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955129538&partnerID=8YFLogxK

U2 - 10.1111/j.1460-9568.2010.07298.x

DO - 10.1111/j.1460-9568.2010.07298.x

M3 - Article

VL - 32

SP - 359

EP - 367

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 3

ER -