Skip to main content

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

  • Conference paper
  • First Online:
The Basal Ganglia IX

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 58))

  • 1014 Accesses

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams JC (1981) Heavy metal intensification of DAB-based HRP reaction product. J Histochem Cytochem 29: 775.

    CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • Barnard EA, Darlison MG and Seeburg P (1987) Molecular biology of the GABAA receptor: The receptor/channel superfamily. Trends Neurosci 10: 502–509.

    Article  CAS  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Bolam JP, Hanley JJ, Booth PA and Bevan MD (2000) Synaptic organisation of the basal ganglia. J Anat 196: 527–542.

    Article  CAS  PubMed  Google Scholar 

  • Boyes J and Bolam JP (2007) Localization of GABA receptors in the basal ganglia. Prog Brain Res 160: 229–243.

    Article  CAS  PubMed  Google Scholar 

  • Colquhoun D and Sivilotti LG (2004) Function and structure in glycine receptors and some of their relatives. Trends Neurosci 27: 337–344.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Graybiel AM (1983) Compartmental organization of the mammalian striatum. Progr Brain Res 58: 247–256.

    Article  CAS  Google Scholar 

  • Graybiel AM (1995) The basal ganglia. Trends Neurosci 18: 60–62.

    Article  CAS  PubMed  Google Scholar 

  • Hornykiewicz O (2001) Chemical neuroanatomy of the basal ganglia - normal and in Parkinson’s disease. J Chem Neuroanat 22: 3–12.

    Article  CAS  PubMed  Google Scholar 

  • Koos T and Tepper JM (1999) Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 2: 467–472.

    Article  CAS  PubMed  Google Scholar 

  • Mai J, Paxinos G and Assheuer J (2003) Atlas of the Human Brain. Academic, New York, NY.

    Google Scholar 

  • McCormick DA, Huguenard JR, Bal T and Pape HC (1997) In Steriade M, Jones EG and McCormick D (Eds) Thalamus. Oxford, Elsevier.

    Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Pisani A, Bernardi G, Ding J and Surmeier DJ (2007) Re-emergence of striatal cholinergic interneurons in movement disorders. Trends Neurosci 30: 545–553.

    Article  CAS  PubMed  Google Scholar 

  • Rajendra S, Lynch JW and Schofield PR (1997) The glycine receptor. Pharmacol Ther 73: 121–146.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Windels F and Kiyatkin EA (2006) GABAergic mechanisms in regulating the activity state of substantia nigra pars reticulata neurons. Neuroscience 140: 1289–1299.

    Article  CAS  PubMed  Google Scholar 

  • 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 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Henry J. Waldvogel .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this paper

Cite this paper

Waldvogel, H.J., Baer, K., Gilbert, R.T., Gai, W., Rees, M.I., Faull, R.L.M. (2009). The Cellular Localisation of GABAA and Glycine Receptors in the Human Basal Ganglia. In: Groenewegen, H., Voorn, P., Berendse, H., Mulder, A., Cools, A. (eds) The Basal Ganglia IX. Advances in Behavioral Biology, vol 58. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0340-2_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-0340-2_18

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-0339-6

  • Online ISBN: 978-1-4419-0340-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics