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Journal of Neuroscience, Vol 16, 283-297, Copyright © 1996 by Society for Neuroscience
Laminar compartmentalization of GABAA-receptor subtypes in the spinal cord: an immunohistochemical study
S Bohlhalter, O Weinmann, H Mohler and JM Fritschy
Institute of Pharmacology, University of Zurich, Switzerland.
To assess the significance of GABAA-receptor heterogeneity, which is based
on a family of at least 15 subunits, the cellular localization and subunit
composition of GABAA-receptor subtypes were analyzed immunohistochemically
in the rat spinal cord. The distribution of subunits alpha 1, alpha 2,
alpha 3, alpha 5, beta 2,3, and gamma 2 was investigated with
subunit-specific antibodies, and their colocalization within individual
neurons was visualized by double-immunofluorescence staining. The results
reveal a widespread expression of the subunits, alpha 3, beta 2,3, and
gamma 2 in the spinal cord, whereas the three other alpha subunits
displayed a more restricted, lamina-specific distribution. The alpha 1 and
alpha 5 subunits were most abundant in the intermediate zone, whereas the
alpha 2 subunit was predominant in the superficial layers of the dorsal
horn and in somatic and preganglionic motoneurons. From colocalization
studies, seven subunit combinations could be identified (alpha 3/beta
2,3/gamma 2; alpha 2/beta 2,3/gamma 2; alpha 1/beta 2,3/gamma 2; alpha
5/beta 2,3/gamma 2; alpha 1/alpha 5/beta 2,3/gamma 2; alpha 2/gamma 2;
alpha 2/alpha 5/gamma 2) that correspond presumably to distinct receptor
subtypes. Although most neurons expressed the subunit triplet alpha x/beta
2,3/gamma 2, the beta 2,3 subunits could not be detected in motoneurons
that may thus possess "atypical" receptor subtypes (alpha 2/gamma 2 and
alpha 2/alpha 5/gamma 2). ON the subcellular level, aggregates of
immunoreactivity, suggestive of postsynaptic GABAA receptors, typically
were seen on the surface of neuronal somata and proximal dendrites. In
addition, an intense diffuse staining was observed in laminae I--III for
the subunits alpha 2, alpha 3, beta 2,3, and gamma 2, presumably localized
on primary afferent terminals. The localization of GABAA- receptor subtypes
in distinct laminar compartments of the spinal cord suggests that
GABAA-receptor heterogeneity is of relevance for the modulation of sensory
inputs, nociception, and motor control at segmental levels.
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