SELECTIVE CLUSTERING OF GABA(A) AND GLYCINE RECEPTORS IN THE MAMMALIAN RETINA

Molecular cloning has revealed a multiplicity of neurotransmitter rece ptor isoforms with different subunit compositions. Additionally, there is growing evidence that such receptors are clustered at postsynaptic sites of neurons. Thus, the questions arise whether individual neuron s express different receptor isoforms and, if so, whether different is oforms are present within the same cluster or are aggregated al distin ct postsynaptic sites. We have studied with immunofluorescence methods and antibodies that recognize specific subunits the distribution of g lycine and GABA(A) receptors in mammalian retinae. Alpha ganglion cell s were injected in rat or rabbit retinae with a fluorescent marker and then immunostained for receptor localization. Clusters of glycine rec eptors and clusters of the alpha 1, alpha 2, alpha 3, and gamma 2 subu nits of the GABA(A) receptor were found on the somatodendritic membran es of Alpha ganglion cells. Double-immunofluorescence experiments with different combinations of the subunit-specific antibodies showed that the alpha 1, alpha 2, and alpha 3 subunits of the GABA(A) receptor ar e not colocalized within the same clusters. These results indicate tha t an individual neuron can express several isoforms of the GABA(A) rec eptor and that these different isoforms are aggregated at distinct pos tsynaptic sites. This suggests individual sorting mechanisms of GABA(A ) receptors at GABAergic synapses.