Advertisement

The Cellular Localisation of GABAA and Glycine Receptors in the Human Basal Ganglia

  • Henry J. Waldvogel
  • Kristin Baer
  • Ray T. Gilbert
  • Weiping Gai
  • Mark I. Rees
  • Richard L. M. Faull
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 58)

Abstract

We have investigated the cellular localisation of GABAA (GABAAR) and glycine (GLYR) receptors in the human basal ganglia using immunohistochemical techniques and light and confocal laser scanning microscopy. GABAAR were most highly expressed on GABAergic striatal interneurons (α1, β2,3, γ2 subunits), cholinergic interneurons (α3), and striatal projection neurons (α2, α3, β2,3, γ2 subunits). GLYR were present mainly on ChAT and a subset of parvalbumin striatal interneurons. The neurons of the globus pallidus (GP) showed high levels of α1, α3, β2,3, γ2 subunits (no α2) whereas GLYRs were only distributed on a subpopulation of pallidal neurons. In addition, GLYRs selectively stained neurons in the intermedullary laminae of the GP. Neurons in the SNr and SNc were labelled with GLYR but had different GABAAR subunit configurations. SNr neurons expressed α1, α3, β2,3, γ2 (no α2) subunits and SNc neurons expressed mainly GABAAR α3γ2 subunits. These results demonstrate that in the basal ganglia, neurons are generally associated with one of four different GABAA receptor configurations. This suggests that throughout the basal ganglia GABA acts via GABAA receptors with various subunit combinations and that glycine acts through glycine receptors on neurons of the SNr and SNc and groups of interneurons scattered throughout the striatum and GP.

Keywords

GABAA Receptor Globus Pallidus Projection Neuron Glycine Receptor Medium Spiny Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by grants from the Neurological Foundation of New Zealand and the Health Research Council of New Zealand. KB is grateful for support from the British Royal Society. We thank the Neurological Foundation of New Zealand Human Brain Bank for providing the human brain tissue used in these studies. We also thank the Biomedical Imaging Research Unit (BIRU) in the Department of Anatomy with Radiology University of Auckland for expert assistance and use of their facilities.

References

  1. Adams JC (1981) Heavy metal intensification of DAB-based HRP reaction product. J Histochem Cytochem 29: 775.PubMedGoogle Scholar
  2. Barnard EA, Stephenson FA, Sigel E, Mamalaki C, Bilbe G, Constanti A, Smart TG and Brown DA (1984) Structure and properties of the brain GABA/benzodiazepine receptor complex. Adv Exp Med Biol 175: 235–254.PubMedGoogle Scholar
  3. Barnard EA, Darlison MG and Seeburg P (1987) Molecular biology of the GABAA receptor: The receptor/channel superfamily. Trends Neurosci 10: 502–509.CrossRefGoogle Scholar
  4. Benke D, Mertens S, Trzeciak A, Gillessen D and Mohler H (1991) GABAA receptors display association of gamma 2-subunit with alpha 1- and beta 2/3-subunits. J Biol Chem 266: 4478–4483.PubMedGoogle Scholar
  5. Benke D, Honer M, Michel C and Mohler H (1996) Gaba(a) receptor subtypes differentiated by their gamma-subunit variants – prevalence, pharmacology and subunit architecture. Neuropharmacology 35: 1413–1423.CrossRefPubMedGoogle Scholar
  6. Benke D, Fakitsas P, Roggenmoser C, Michel C, Rudolph U and Mohler H (2004) Analysis of the presence and abundance of GABA(A) receptors containing two different types of alpha subunits in murine brain using point-mutated alpha subunits. J Biol Chem 279: 43654–43660.CrossRefPubMedGoogle Scholar
  7. Bolam JP, Hanley JJ, Booth PA and Bevan MD (2000) Synaptic organisation of the basal ganglia. J Anat 196: 527–542.CrossRefPubMedGoogle Scholar
  8. Boyes J and Bolam JP (2007) Localization of GABA receptors in the basal ganglia. Prog Brain Res 160: 229–243.CrossRefPubMedGoogle Scholar
  9. Colquhoun D and Sivilotti LG (2004) Function and structure in glycine receptors and some of their relatives. Trends Neurosci 27: 337–344.CrossRefPubMedGoogle Scholar
  10. Darbin O and Wichmann T (2008) Effects of striatal GABA-A receptor blockade on striatal and cortical activity in monkeys. J Neurophysiol. 99:1294–1305.CrossRefPubMedGoogle Scholar
  11. Darstein M, Loschmann PA, Knorle R and Feuerstein TJ (1997) Strychnine-sensitive glycine receptors inducing [3H]-acetylcholine release in rat caudatoputamen: A new site of action of ethanol? Naun Schmied Arch Pharmacol 356: 738–745.CrossRefGoogle Scholar
  12. Darstein M, Landwehrmeyer GB, Kling C, Becker CM and Feuerstein TJ (2000) Strychnine-sensitive glycine receptors in rat caudatoputamen are expressed by cholinergic interneurons. Neuroscience 96: 33–39.CrossRefPubMedGoogle Scholar
  13. Ericson M, Molander A, Stomberg R and Soderpalm B (2006) Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. Eur J Neurosci 23: 3225–3229.CrossRefPubMedGoogle Scholar
  14. Fritschy JM and Mohler H (1995) GABA(A)-receptor heterogeneity in the adult rat brain - Differential regional and cellular distribution of seven major subunits. J Comp Neurol 359: 154–194.CrossRefPubMedGoogle Scholar
  15. Fritschy JM, Weinmann O, Wenzel A and Benke D (1998) Synapse-specific localization of NMDA and GABA(A) receptor subunits revealed by antigen-retrieval immunohistochemistry. J Comp Neurol 390: 194–210.CrossRefPubMedGoogle Scholar
  16. Fujiyama F, Fritschy JM, Stephenson FA and Bolam JP (2000) Synaptic localization of GABA(A) receptor subunits in the striatum of the rat. J Comp Neurol 416: 158–172.CrossRefPubMedGoogle Scholar
  17. Gao B, Fritschy JM, Benke D and Mohler H (1993) Neuron-specific expression of GABAA-receptor subtypes: Differential association of the a1 and a3-subunits with serotonergic and GABAergic neurons. Neuroscience 54: 881–892.CrossRefPubMedGoogle Scholar
  18. Graybiel AM (1983) Compartmental organization of the mammalian striatum. Progr Brain Res 58: 247–256.CrossRefGoogle Scholar
  19. Graybiel AM (1995) The basal ganglia. Trends Neurosci 18: 60–62.CrossRefPubMedGoogle Scholar
  20. Hornykiewicz O (2001) Chemical neuroanatomy of the basal ganglia - normal and in Parkinson’s disease. J Chem Neuroanat 22: 3–12.CrossRefPubMedGoogle Scholar
  21. Koos T and Tepper JM (1999) Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 2: 467–472.CrossRefPubMedGoogle Scholar
  22. Mai J, Paxinos G and Assheuer J (2003) Atlas of the Human Brain. Academic, New York, NY.Google Scholar
  23. McCormick DA, Huguenard JR, Bal T and Pape HC (1997) In Steriade M, Jones EG and McCormick D (Eds) Thalamus. Oxford, Elsevier.Google Scholar
  24. Pfeiffer F, Simler R, Grenningloh G and Betz H (1984) Monoclonal antibodies and peptide mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord. Proc Natl Acad Sci USA 81: 7224–7227.CrossRefPubMedGoogle Scholar
  25. Pirker S, Schwarzer C, Wieselthaler A, Sieghart W and Sperk G (2000) GABA(A) receptors: Immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101: 815–850.CrossRefPubMedGoogle Scholar
  26. Pisani A, Bernardi G, Ding J and Surmeier DJ (2007) Re-emergence of striatal cholinergic interneurons in movement disorders. Trends Neurosci 30: 545–553.CrossRefPubMedGoogle Scholar
  27. Rajendra S, Lynch JW and Schofield PR (1997) The glycine receptor. Pharmacol Ther 73: 121–146.CrossRefPubMedGoogle Scholar
  28. Schroder S, Hoch W, Becker CM, Grenningloh G and Betz H (1991) Mapping of antigenic epitopes on the alpha 1 subunit of the inhibitory glycine receptor. Biochem 30: 42–47.CrossRefGoogle Scholar
  29. Smith Y, Bevan MD, Shink E and Bolam JP (1998) Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86: 353–387.CrossRefPubMedGoogle Scholar
  30. Smith Y, Charara A, Paquet M, Kieval JZ, Pare JF, Hanson JE, Hubert GW, Kuwajima M and Levey AI (2001) Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia. J Chem Neuroanat 22:13–42.CrossRefPubMedGoogle Scholar
  31. Waldvogel HJ, Kubota Y, Fritschy JM, Mohler H and Faull RLM (1999) Regional and cellular localisation of GABA(A) receptor subunits in the human basal ganglia: An autoradiographic and immunohistochemical study. J Comp Neurol 415: 313–340.CrossRefPubMedGoogle Scholar
  32. Waldvogel HJ, Billinton A, White JH, Emson PC and Faull RL (2004) Comparative cellular distribution of GABAA and GABAB receptors in the human basal ganglia: Immunohistochemical colocalization of the alpha 1 subunit of the GABAA receptor, and the GABABR1 and GABABR2 receptor subunits. J Comp Neurol 470: 339–356.CrossRefPubMedGoogle Scholar
  33. Waldvogel HJ, Curtis MA, Baer K, Rees MI and Faull RL (2006) Immunohistochemical staining of post-mortem adult human brain sections. Nat Protoc 1: 2719–2732.CrossRefPubMedGoogle Scholar
  34. Waldvogel HJ, Baer K, Allen KL, Rees MI and Faull RL (2007) Glycine receptors in the striatum, globus pallidus, and substantia nigra of the human brain: An immunohistochemical study. J Comp Neurol 502: 1012–1029.CrossRefPubMedGoogle Scholar
  35. Waldvogel HJ, Baer K, Gai WP, Gilbert RT, Rees MI, Mohler H and Faull RL (2008) Differential localization of GABA(A) receptor subunits within the substantia nigra of the human brain: An immunohistochemical study. J Comp Neurol 506: 912–929.CrossRefPubMedGoogle Scholar
  36. Windels F and Kiyatkin EA (2006) GABAergic mechanisms in regulating the activity state of substantia nigra pars reticulata neurons. Neuroscience 140: 1289–1299.CrossRefPubMedGoogle Scholar
  37. Woolsey T (2003) In Woolsey T, Hanaway J, and Gado M (Eds) The Brain Atlas: A Visual Guide to the Central Nervous System, 2nd ed. Wiley, Hoboken, NJ.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Henry J. Waldvogel
    • 1
  • Kristin Baer
    • 1
  • Ray T. Gilbert
    • 1
  • Weiping Gai
    • 1
  • Mark I. Rees
    • 1
  • Richard L. M. Faull
    • 1
  1. 1.Department of Anatomy with Radiology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand

Personalised recommendations