THE ALPHA-6 SUBUNIT OF THE GABA(A) RECEPTOR IS CONCENTRATED IN BOTH INHIBITORY AND EXCITATORY SYNAPSES ON CEREBELLAR GRANULE CELLS

Although three distinct subunits seem to be sufficient to form a funct ional pentameric GABA(A) receptor channel, cerebellar granule cells ex press mRNA for nine subunits. They receive GABAergic input from a rela tively homogeneous 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 re sulting in distinct types of synaptic and/or extrasynaptic channels. A ntibodies to different parts of the alpha 6 and alpha 1 subunits of th e GABA(A) receptor and electron microscopic immunogold localization we re used to determine the precise subcellular distribution of these sub units in relation to specific synaptic inputs. Both subunits were pres ent in the extrasynaptic dendritic and somatic membranes at lower dens ities than in synaptic junctions. The alpha 6 and alpha 1 subunits wer e colocalized in many GABAergic Golgi synapses, demonstrating that bot h subunits are involved in synaptic transmission in the same synapse. Synapses immunopositive for only one of the alpha subunits were also f ound. The alpha 6, but not the alpha 1, subunit was also concentrated in glutamatergic messy fiber synapses, indicating that the alpha 6 sub unit may have several roles depending on its different locations. The results demonstrate a partially differential synaptic targeting of two distinct GABA(A) receptor subunits on the surface of the same type of neuron.