Neuron-specific expression of GABAA-receptor subtypes: differential association of the alpha 1- and alpha 3-subunits with serotonergic and GABAergic neurons.
GABAA-receptors in the brain display a striking structural heterogeneity, which is based on a multiplicity of diverse subunits. The allocation of GABAA-receptor subtypes to identified neurons is essential for an analysis of the functional significance of receptor heterogeneity. Among GABA-receptive neurons, well-characterized examples include the serotonergic and GABAergic neurons in the raphe nuclei. The GABAA-receptor subtypes expressed in these two types of neurons were analysed using antisera which recognize selectively the alpha 1- and alpha 3-subunits, and their co-localization with serotonin and glutamate decarboxylase was assessed by confocal laser microscopy in double and triple immunofluorescence staining in the rat. The vast majority of serotonergic neurons express strong alpha 3-subunit-immunoreactivity, but are devoid of alpha 1-subunit staining. In contrast, both the alpha 1- and alpha 3-subunit-immunoreactivities are present in glutamate decarboxylase-positive neurons. Thus, serotonergic and GABAergic neurons selectively express distinct patterns of alpha subunits, suggesting that they possess distinct subtypes of GABAA-receptors. The occurrence of neuron-specific GABAA-receptor subtypes may open new possibilities for the targeting of drugs with selective therapeutic actions.
Institute of Pharmacology, University of Zurich, Switzerland.
B
B
Gao
J M
JM
Fritschy
D
D
Benke
H
H
Mohler
D000818:Animals; D000918:Antibody Specificity; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D005968:Glutamate Decarboxylase / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007834:Lasers; D008297:Male; D008853:Microscopy; D009474:Neurons / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000276:immunology; D012701:Serotonin / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase