Home LiteratureArticle Details
PMID: 8876241 Published · ppublish English Journal Article

Differential synaptic localization of two major gamma-aminobutyric acid type A receptor alpha subunits on hippocampal pyramidal cells.

Nusser Z, Sieghart W, Benke D, Fritschy JM, Somogyi P

Abstract

Hippocampal pyramidal cells, receiving domain specific GABAergic inputs, express up to 10 different subunits of the gamma-aminobutyric acid type A (GABAA) receptor, but only 3 different subunits are needed to form a functional pentameric channel. We have tested the hypothesis that some subunits are selectively located at subsets of GABAergic synapses. The alpha 1 subunit has been found in most GABAergic synapses on all postsynaptic domains of pyramidal cells. In contrast, the alpha 2 subunit was located only in a subset of synapses on the somata and dendrites, but in most synapses on axon initial segments innervated by axo-axonic cells. The results demonstrate that molecular specialization in the composition of postsynaptic GABAA receptor subunits parallels GABAergic cell specialization in targeting synapses to a specific domain of postsynaptic cortical neurons.

MeSH Terms
Animals Axons/metabolism,ultrastructure Dendrites/metabolism,ultrastructure Hippocampus/metabolism Immune Sera Macromolecular Substances Microscopy, Immunoelectron Pyramidal Cells/metabolism,ultrastructure Rats Rats, Wistar Receptors, GABA-A/analysis,metabolism Synapses/metabolism,ultrastructure
Chemicals
Immune Sera Macromolecular Substances Receptors, GABA-A
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Nusser Z
Anatomical Neuropharmacology Unit, University of Oxford, United Kingdom.
Sieghart W
Benke D
Fritschy J M
Somogyi P
References (44)
44 references, click to expand
  1. The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon.
    J Neurosci. 1992 Mar;12(3):1040-62 PMID: 1312131
  2. Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes.
    Pharmacol Rev. 1995 Jun;47(2):181-234 PMID: 7568326
  3. Comparative molecular neuroanatomy of cloned GABAA receptor subunits in the rat CNS.
    J Comp Neurol. 1992 Dec 8;326(2):193-216 PMID: 1336019
  4. Assembly of GABAA receptor subunits determines sorting and localization in polarized cells.
    Nature. 1993 Feb 4;361(6411):457-60 PMID: 8381522
  5. GABAA-receptors: drug binding profile and distribution of receptors containing the alpha 2-subunit in situ.
    J Recept Res. 1993;13(1-4):467-77 PMID: 8383760
  6. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction.
    Neuron. 1993 Oct;11(4):771-87 PMID: 8104433
  7. Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons.
    Nature. 1993 Dec 23-30;366(6457):745-8 PMID: 8264797
  8. Distribution of GABAergic synapses and their targets in the dentate gyrus of rat: a quantitative immunoelectron microscopic analysis.
    J Hirnforsch. 1993;34(3):299-308 PMID: 8270784
  9. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites.
    Nature. 1994 Jan 6;367(6458):69-72 PMID: 8107777
  10. Precision and variability in postsynaptic target selection of inhibitory cells in the hippocampal CA3 region.
    Eur J Neurosci. 1993 Dec 1;5(12):1729-51 PMID: 8124523
  11. Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites.
    Nature. 1994 Apr 28;368(6474):823-8 PMID: 8159242
  12. GABAA receptor channels.
    Annu Rev Neurosci. 1994;17:569-602 PMID: 7516126
  13. Activation of metabotropic glutamate receptors differentially affects two classes of hippocampal interneurons and potentiates excitatory synaptic transmission.
    J Neurosci. 1994 Jul;14(7):4433-45 PMID: 7517996
  14. Distribution, prevalence, and drug binding profile of gamma-aminobutyric acid type A receptor subtypes differing in the beta-subunit variant.
    J Biol Chem. 1994 Oct 28;269(43):27100-7 PMID: 7929453
  15. Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat.
    J Neurosci. 1995 Jan;15(1 Pt 1):47-60 PMID: 7823151
  16. The cisternal organelle as a Ca(2+)-storing compartment associated with GABAergic synapses in the axon initial segment of hippocampal pyramidal neurones.
    Exp Brain Res. 1994;101(2):216-30 PMID: 7843310
  17. Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells.
    Hippocampus. 1995;5(1):78-90 PMID: 7787949
  18. Immunocytochemical localization of the alpha 1 and beta 2/3 subunits of the GABAA receptor in relation to specific GABAergic synapses in the dentate gyrus.
    Eur J Neurosci. 1995 Apr 1;7(4):630-46 PMID: 7620614
  19. GABAA/benzodiazepine receptor heterogeneity: neurophysiological implications.
    Neuropharmacology. 1995 Mar;34(3):245-54 PMID: 7630479
  20. The GABAA receptors.
    Biochem J. 1995 Aug 15;310 ( Pt 1):1-9 PMID: 7646429
  21. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons.
    Nature. 1995 Nov 2;378(6552):75-8 PMID: 7477292
  22. Properties of unitary IPSPs evoked by anatomically identified basket cells in the rat hippocampus.
    Eur J Neurosci. 1995 Sep 1;7(9):1989-2004 PMID: 8528474
  23. The alpha 6 subunit of the GABAA receptor is concentrated in both inhibitory and excitatory synapses on cerebellar granule cells.
    J Neurosci. 1996 Jan;16(1):103-14 PMID: 8613776
  24. Selective clustering of GABA(A) and glycine receptors in the mammalian retina.
    J Neurosci. 1996 Mar 15;16(6):2127-40 PMID: 8604056
  25. Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization.
    J Neurophysiol. 1961 May;24:225-42 PMID: 13751136
  26. Recurrent inhibition in the hippocampus with identification of the inhibitory cell and its synapses.
    Nature. 1963 May 11;198:540-2 PMID: 14012800
  27. PATHWAY OF POSTSYNAPTIC INHIBITION IN THE HIPPOCAMPUS.
    J Neurophysiol. 1964 Jul;27:608-19 PMID: 14194961
  28. The axon initial segment as a synaptic site: ultrastructure and synaptology of the initial segment of the pyramidal cell in the rat hippocampus (CA3 region).
    J Neurocytol. 1980 Dec;9(6):861-82 PMID: 7205337
  29. Affinity-purified anti-protein I antibody. Specific inhibitor of phosphorylation of protein I, a synaptic protein.
    J Biol Chem. 1981 Oct 25;256(20):10657-63 PMID: 6793584
  30. A new type of specific interneuron in the monkey hippocampus forming synapses exclusively with the axon initial segments of pyramidal cells.
    Brain Res. 1983 Jan 17;259(1):137-42 PMID: 6824927
  31. Unitary inhibitory synaptic potentials in the guinea-pig hippocampus in vitro.
    J Physiol. 1984 Nov;356:97-113 PMID: 6097680
  32. Distribution of glycine receptors at central synapses: an immunoelectron microscopy study.
    J Cell Biol. 1985 Aug;101(2):683-8 PMID: 2991304
  33. Cholecystokinin-immunoreactive cells form symmetrical synaptic contacts with pyramidal and nonpyramidal neurons in the hippocampus.
    J Comp Neurol. 1985 Jul 22;237(4):485-505 PMID: 4044896
  34. Inhibitory control of local excitatory circuits in the guinea-pig hippocampus.
    J Physiol. 1987 Jul;388:611-29 PMID: 3656200
  35. GABAergic neurons containing the Ca2+-binding protein parvalbumin in the rat hippocampus and dentate gyrus.
    Brain Res. 1987 Sep 1;419(1-2):119-30 PMID: 3315112
  36. Stratum lacunosum-moleculare interneurons of hippocampal CA1 region. I. Intracellular response characteristics, synaptic responses, and morphology.
    J Neurosci. 1988 Apr;8(4):1400-10 PMID: 3357023
  37. Physiological heterogeneity of nonpyramidal cells in rat hippocampal CA1 region.
    Exp Brain Res. 1988;72(3):494-502 PMID: 3234499
  38. Type I and type II GABAA-benzodiazepine receptors produced in transfected cells.
    Science. 1989 Sep 22;245(4924):1389-92 PMID: 2551039
  39. Proportion of parvalbumin-positive basket cells in the GABAergic innervation of pyramidal and granule cells of the rat hippocampal formation.
    J Comp Neurol. 1990 Oct 22;300(4):449-61 PMID: 2273087
  40. GABA autoreceptors regulate the induction of LTP.
    Nature. 1991 Feb 14;349(6310):609-11 PMID: 1847993
  41. Separation of alpha 1, alpha 2 and alpha 3 subunits of the GABAA-benzodiazepine receptor complex by immunoaffinity chromatography.
    Brain Res. 1991 Nov 1;563(1-2):325-8 PMID: 1664775
  42. GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.
    J Comp Neurol. 1995 Aug 14;359(1):154-94 PMID: 8557845
  43. Hippocampal CA1 interneurons: an in vivo intracellular labeling study.
    J Neurosci. 1995 Oct;15(10):6651-65 PMID: 7472426
  44. Quantitative distribution of GABA-immunopositive and -immunonegative neurons and synapses in the monkey striate cortex (area 17).
    Cereb Cortex. 1992 Jul-Aug;2(4):295-309 PMID: 1330121
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1996-10-15
Pages
11939-44
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38162
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com