Skip to main content
Log in

Differences in expression of GABAA receptor subunits, but not benzodiazepine binding, in the chick brainstem auditory system

  • Original Articles
  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Neurons in nucleus magnocellularis (NM) and nucleus laminaris (NL) of the chick brainstem auditory system show an unusual physiological response to GABA. Examination of these nuclei usingin situ hybridization for GABAA receptor subunits showed a differential expression of the γ2 and α1 subunits. The γ2 subunit was found in both NM and NL, but the α1 subunit was found in NL only. Like NL, other areas of the tissue section that showed labeling with the γ2 probe, such as the medial vestibular nucleus (VeM) and granule cells of the cerebellum (CB), also labeled with the α1 probe. Thus, given that NM labeled with the γ2 probe, the absence of the α1 subunit was unusual in this tissue. This difference in subunit composition suggests that there may also be a difference in GABA receptor function in NM compared to these neighboring areas. One feature of the GABAA receptor believed to be related to the presence of γ2 and α1 subunits is specific pharmacological properties of the benzodiazepine modulatory site. It has been proposed that the α1 subunit is necessary for producing a GABAA receptor with a benzodiazepine site that has Type I binding characteristics. The present experiments challenge this hypothesis. Based on the differential presence of the α1 subunit, one would expect that GABA receptors in NM would show different benzodiazepine binding properties than NL, VeM, and CB. However, displacement of3H-flunitrazepam binding using CL 218,872, which differentiates between the Type I and Type II receptors, showed no difference between these areas. Additionally, the relatively high affinity for CL 218,872 suggests that even NM contains Type I receptors.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Barnard E. A. (1992) Receptor classes and the transmitter-gated ion channels.Trends Biochem. Sci. 17, 368–374.

    Article  PubMed  CAS  Google Scholar 

  • Barnard E. A. (1995) The molecular biology of GABAA receptors and their structural determinants, inGABA A Receptors and Anxiety: From Neurobiology to Treatment (Biggio G., Sanna E., and Costa E., eds.), Raven, New York, 1–16.

    Google Scholar 

  • Barnard E. A., Darlison M. G., and Seeburg P. (1987) Molecular biology of the GABAA receptor: the receptor/channel superfamily.Trends Neurosci. 10, 502–509.

    Article  CAS  Google Scholar 

  • Bateson A. N., Harvey R. J., Wisden W., Glencorse T. A., Hicks A. A., Hunt S. P., Barnard E. A., and Darlison M. G. (1991a) The chicken GABAA receptor α1 subunit: cDNA sequence and localization of the corresponding mRNA.Mol. Brain Res. 9, 333–339.

    Article  PubMed  CAS  Google Scholar 

  • Bateson A. N., Lasham A., and Darlison M. G. (1991b) Gamma-aminobutyric acidA receptor heterogeneity is increased by alternative splicing of a novel beta-subunit gene transcript.J. Neurochem. 56, 1437–1440.

    Article  PubMed  CAS  Google Scholar 

  • Code R. A. and Churchill L. (1991) GABAA receptors in auditory brainstem nuclei of the chick during development and after cochlea removal.Hear. Res. 54, 281–295.

    Article  PubMed  CAS  Google Scholar 

  • Code R. A., Burd G. D., and Rubel E. W. (1989) Development of GABA-immunoreactivity in brain stem auditory nuclei of the chick: ontogeny of gradients in terminal staining.J. Comp. Neurol. 284, 504–518.

    Article  PubMed  CAS  Google Scholar 

  • Costa E. and Guidotti A. (1996) Benzodiazepines on trial: a research strategy for their rehabilitation.Trends Pharmacol. Sci. 17, 192–200.

    Article  PubMed  CAS  Google Scholar 

  • Doble A. and Martin I. L. (1992) Multiple benzodiazepine receptors: no reason for anxiety.Trends Pharmacol. Sci. 13, 76–81.

    Article  PubMed  CAS  Google Scholar 

  • Glencorse T. A., Bateson A. N., and Darlison M. G. (1990) Sequence of the chicken GABAA receptor γ2-subunit cDNA.Nucleic Acids Res. 18, 7157.

    Article  PubMed  CAS  Google Scholar 

  • Glencorse T. A., Bateson A. N., Hunt S. P., and Darlison M. G. (1991) Distribution of the GABAA receptor alpha 1- and gamma 2-subunit mRNAs in chick brain.Neurosci. Lett. 133, 45–48.

    Article  PubMed  CAS  Google Scholar 

  • Glencorse T. A., Darlison M. G., Barnard E. A., and Bateson A. N. (1993) Sequence and novel distribution of the chicken homologue of the mammalian gamma-aminobutyric acidA receptor gamma 1 subunit.J. Neurochem. 61, 2294–2302.

    Article  PubMed  CAS  Google Scholar 

  • Harvey R. J., Kim H. C., and Darlison M. G. (1993) Molecular cloning reveals the existence of a fourth gamma subunit of the vertebrate brain GABAA receptor.FEBS Lett. 331, 211–216.

    Article  PubMed  CAS  Google Scholar 

  • Hyson R. L., Reyes A. D., and Rubel E. W (1995) A depolarizing inhibitory response to GABA in brain stem auditory neurons of the chick.Brain Res. 677, 117–126.

    Article  PubMed  CAS  Google Scholar 

  • Joseph A. W. and Hyson R. L. (1993) Coincidence detection by binaural neurons in the chick brain stem.J. Neurophysiol. 69, 1197–1211.

    PubMed  CAS  Google Scholar 

  • Klepner C. A., Lippa A. S., Bensen D. I., Sano M. C., and Beer B. (1979) Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors.Pharmacol. Biochem. Behav. 11, 457–462.

    Article  PubMed  CAS  Google Scholar 

  • Lachica E. A., Rübsamen R., and Rubel E. W (1994) GABAergic terminals in nucleus magnocellularis and laminaris originate from the superior olivary nucleus.J. Comp. Neurol. 348, 403–418.

    Article  PubMed  CAS  Google Scholar 

  • Lasham A., Vreugdenhil E., Bateson A. N., Barnard E. A., and Darlison M. G. (1991) Conserved organization of gamma-aminobutyric acidA receptor genes: cloning and analysis of the chicken beta 4-subunit gene.J. Neurochem. 57, 352–355.

    Article  PubMed  CAS  Google Scholar 

  • Lippa A. S., Beer B., Sano M. C., Vogel R. A., and Meyerson L. R. (1981) Differential ontogeny of type 1 and type 2 benzodiazepine receptors.Life Sci. 28, 2343–2347.

    Article  PubMed  CAS  Google Scholar 

  • McKernan R. M. and Whiting P. J. (1996) Which GABAA-receptor subtypes really occur in the brain?Trends Neurosci. 19, 139–143.

    Article  PubMed  CAS  Google Scholar 

  • Mihic S. J., Whiting P. J., Klein R. L., Wafford K. A. and Harris R. A. (1994) A single amino acid of the human γ-aminobutyric acid type A receptor γ2 subunit determines benzodiazepine efficacy.J. Biol. Chem. 269, 32,768–32,773.

    CAS  Google Scholar 

  • Nayeem N., Green T. P., Martin I. L., and Barnard E. A. (1994) Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis.J. Neurochem. 62, 815–818.

    Article  PubMed  CAS  Google Scholar 

  • Olsen R. W. and Tobin A. J. (1990) Molecular biology of GABAA receptors.FASEB 4, 1469–1480.

    CAS  Google Scholar 

  • Overholt E. M., Rubel E. W, and Hyson R. L. (1992) A circuit for coding interaural time differences in the chick brainstem.J. Neurosci. 12, 1698–1708.

    PubMed  CAS  Google Scholar 

  • Pritchett D. B. and Seeburg P. H. (1990) γ-Aminobutyric acidA receptor α5-subunit creates novel type II benzodiazepine receptor pharmacology.J. Neurochem. 54, 1802–1804.

    Article  PubMed  CAS  Google Scholar 

  • Pritchett D. B. and Seeburg P. H. (1991) γ-Aminobutyric acid type A receptor point mutation increases the affinity of compounds for the benzodiazepine site.Proc. Natl. Acad. Sci. USA 88, 1421–1425.

    Article  PubMed  CAS  Google Scholar 

  • Pritchett D. B., Luddens H. H., and Seeburg P. H. (1989a) Type I and type II GABAA-benzodiazepine receptors produced in transfected cells.Science 245, 1389–1392.

    Article  PubMed  CAS  Google Scholar 

  • Pritchett D. B., Sontheimer H., Shivers B., Ymer S., Kettenmann H., Schofield P. R., and Seeburg P. H. (1989b) Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology.Nature 338, 582–585.

    Article  PubMed  CAS  Google Scholar 

  • Rubel E. W and Parks T. N. (1988) Organization and development of the avian brain stem auditory system, inFunctions of the Auditory System (Edelman G. M., Gall, W. E., and Cowan W. M., eds.), John Wiley, New York, pp. 3–92.

    Google Scholar 

  • Rubel E. W, Smith D. H., and Miller L. C. (1976) Organization and development of brain stem auditory nuclei of the chicken: ontogeny of n. magnocellularis and n. laminaris.J. Comp. Neurol. 166, 469–490.

    Article  PubMed  CAS  Google Scholar 

  • Sieghart W. (1992) GABAA receptors: ligand-gated Cl ion channels modulated by multiple drug-binding sites.Trends Pharmacol. Sci. 13, 446–450.

    Article  PubMed  CAS  Google Scholar 

  • Squires R. F., Benson D. I., Braestrup C., Coupet J., Klepner C. A., Myers V., and Beer B. (1979) Some properties of brain specific benzodiazepine receptors: new evidence for multiple receptors.Pharmacol. Biochem. Behav. 10, 825–830.

    Article  PubMed  CAS  Google Scholar 

  • Verdoorn T., Draguhn A., Ymer S., Seeburg P., and Sakmann B. (1990) Functional properties of recombinant rat GABAA receptors depend upon subunit composition.Neuron 4, 919–928.

    Article  PubMed  CAS  Google Scholar 

  • Vicini S. (1991) Pharmacological significance of the structural heterogeneity of the GABAA receptor-chloride ion channel complex.Neuropsychopharmacology 4, 9–15.

    PubMed  CAS  Google Scholar 

  • von Bartheld C. S., Code R. A., and Rubel E. W (1989) GABAergic neurons in brainstem auditory nuclei of the chick: distribution, morphology and connectivity.J. Comp. Neurol. 287, 470–483.

    Article  Google Scholar 

  • Whiting P., McKernan R. M., and Iversen L. L. (1990) Another mechanism for creating diversity in γ-aminobutyrate type A receptors: RNA splicing directs expression of two forms of γ2 subunit, one of which contains a protein kinase C phosphorylation site.Proc. Natl. Acad. Sci. USA 87, 9966–9970.

    Article  PubMed  CAS  Google Scholar 

  • Wieland H. A., Luddens H., and Seeburg P. H. (1992) Molecular determinants in GABAA/BZ receptor subtypes, inGABAergic Synaptic Transmission (Biggio G., Concal A., and Costa E., eds.), Raven, New York, pp. 29–40.

    Google Scholar 

  • Young W. S. III, Niehoff D., Kuhar M. J., Beer B., and Lippa A. S. (1981) Multiple benzodiazepine receptor localization by light microscopic radiohistochemistry.J. Pharmacol. Exp. Ther. 216, 425–430.

    PubMed  Google Scholar 

  • Zhou N. and Parks T. N. (1992a) Developmental changes in the effects of drugs acting at NMDA or non-NMDA receptors on synaptic transmission in the chick cochlear nucleus (nuc. magnocellularis).Dev. Brain Res. 67, 145–152.

    Article  CAS  Google Scholar 

  • Zhou N. and Parks T. N. (1992b) Gamma-d-glutamylaminomethyl sulfonic acid (GAMS) distinguishes subtypes of glutamate receptor in the chick cochlear nucleus (nuc. magnocellularis).Hear. Res. 60, 20–26.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hyson, R.L., Sadler, K.A. Differences in expression of GABAA receptor subunits, but not benzodiazepine binding, in the chick brainstem auditory system. J Mol Neurosci 8, 193–205 (1997). https://doi.org/10.1007/BF02736833

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02736833

Index Entries

Navigation