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Journal of Neuroscience, Vol 16, 103-114, Copyright © 1996 by Society for Neuroscience
The alpha 6 subunit of the GABAA receptor is concentrated in both inhibitory and excitatory synapses on cerebellar granule cells
Z Nusser, W Sieghart, FA Stephenson and P Somogyi
Medical Research Council, Anatomical Neuropharmacology Unit, University of Oxford, United Kingdom.
Although three distinct subunits seem to be sufficient to form a functional
pentameric GABAA receptor channel, cerebellar granule cells express nRNA
for nine subunits. They receive GABAergic input from a relatively
homogenous population of Golgi cells. It is not known whether all subunits
are distributed similarly on the surface of granule cells or whether some
of them have differential subcellular distribution resulting in distinct
types of synaptic and/or extrasynaptic channels. Antibodies to different
parts of the alpha 6 and alpha 1 subunits of the GABAA receptor and
electron microscopic immunogold localization were used to determine the
precise subcellular distribution of these subunits in relation to specific
synaptic inputs. Both subunits were present in the extrasynaptic dendritic
and somatic membranes at lower densities than in synaptic junctions. The
alpha 6 and alpha 1 subunits were colocalized in many GABAergic Golgi
synapses, demonstrating that both subunits are involved in synaptic
transmission in the same synapse. Synapses immunopositive for only one of
the alpha subunits were also found. The alpha 6, but not the alpha 1,
subunit was also concentrated in glutamatergic mossy fiber synapses,
indicating that the alpha 6 subunit may have several roles depending on its
different locations. The results demonstrate a partially differential
synaptic targeting of two distinct GABAA receptor subunits on the surface
of the same type of neuron.
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