Get access

GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization

Authors

  • Jean-Marc Fritschy,

    1. Institute of Pharmacology, Swiss Federal Institute of Technology (ETH) and University of Zürich, CH-8057, Zürich, Switzerland
    Search for more papers by this author
  • Virginia Meskenaite,

    1. Institute of Pharmacology, Swiss Federal Institute of Technology (ETH) and University of Zürich, CH-8057, Zürich, Switzerland
    2. Institute of Neuroinformatics, Swiss Federal Institute of Technology (ETH) and University of Zürich, CH-8006, Zürich, Switzerland
    Search for more papers by this author
  • Oliver Weinmann,

    1. Institute of Pharmacology, Swiss Federal Institute of Technology (ETH) and University of Zürich, CH-8057, Zürich, Switzerland
    Search for more papers by this author
  • Michael Honer,

    1. Institute of Pharmacology, Swiss Federal Institute of Technology (ETH) and University of Zürich, CH-8057, Zürich, Switzerland
    Search for more papers by this author
  • Dietmar Benke,

    1. Institute of Pharmacology, Swiss Federal Institute of Technology (ETH) and University of Zürich, CH-8057, Zürich, Switzerland
    Search for more papers by this author
  • Hanns Mohler

    1. Institute of Pharmacology, Swiss Federal Institute of Technology (ETH) and University of Zürich, CH-8057, Zürich, Switzerland
    Search for more papers by this author

J.-M. Fritschy, as above. E-mail: fritschy@pharma.unizh.ch

Abstract

GABAB (γ-aminobutyric acid)-receptors have been implicated in central nervous system (CNS) functions, e.g. cognition and pain perception, and dysfunctions including spasticity and absence epilepsy. To permit an analysis of the two known GABAB-receptor splice variants GABAB-R1a (GB1a) and GABAB-R1b (GB1b), their distribution pattern has been differentiated in the rat brain, using Western blotting and immunohistochemistry with isoform-specific antisera. During postnatal maturation, the expression of the two splice variants was differentially regulated with GB1a being preponderant at birth. In adult brain, GB1b-immunoreactivity (-IR) was predominant, and the two isoforms largely accounted for the pattern of GABAB-receptor binding sites in the brain. Receptor heterogeneity was pronounced in the hippocampus, where both isoforms occurred in CA1, but only GB1b in CA3. Similarly, in the cerebellum, GB1b was exclusively found in Purkinje cells in a zebrin-like pattern. The staining was most pronounced in Purkinje cell dendrites and spines. Using electron microscopy, over 80% of the spine profiles in which a synaptic contact with a parallel fibre was visible contained GB1b-IR at extrasynaptic sites. This subcellular localization is unrelated to GABAergic inputs, indicating that the role of GABAB-receptors in vivo extends beyond synaptic GABAergic neurotransmission and may, in the cerebellum, involve taurine as a ligand.

Get access to the full text of this article

Ancillary