Mitral cells are the principal neurons of the olfactory bulb. They express high levels of GABAA receptors containing the alpha1 and alpha3 subunits, clustered at reciprocal synapses formed with granule cell dendrites. Here, we investigated whether the specific absence of 1-GABAA receptors in alpha10/0 mice affects GABAergic synapses in mitral cells. We found a marked increase of alpha3 subunit clusters on the cell body of mitral cells of alpha10/0 mice, suggesting that the alpha3 subunit replaces alpha1 in these dendrosomatic synapses. A general increase of alpha3 subunit immunofluorescence was also seen in the external plexiform layer (EPL). However, a quantitative analysis of alpha3 clusters colocalized with gephyrin in the EPL revealed an increase in size, but only a limited increase in density, pointing to partial compensation for the missing alpha1 subunit. Unexpectedly, the number of gephyrin clusters was unchanged, and staining for the alpha2, alpha5, and gamma2 subunits revealed no significant changes in the EPL of alpha10/0 mice. Thus, a fraction of synaptic sites might retain gephyrin while being devoid of GABAA receptors in mutant mice. Despite these changes, the morphology of mitral cells and their postnatal maturation were undistinguishable in wildtype and mutant mice. Ultrastructurally, no difference in morphology of reciprocal synapses was evident between genotypes in the EPL. Gephyrin, as detected by postembedding immunogold labeling, was selectively clustered in GABAergic synapses. However, a strong increase in alpha3 subunit labeling was observed, reflecting the increased cluster size detected in light microscopy. These results indicate that the organization of GABAA receptors is altered in mitral cells of alpha10/0 mice. A single GABAA receptor subtype remains expressed, which partially compensates for the missing 1 subunit, notably in perisomatic reciprocal synapses. In addition, gephyrin clustering appears to be independent of GABAA receptor clustering in a subset of synapses of the mouse EPL.

Reorganization of GABAA receptors, but not gephyrin, in mitral cells of alpha1 subunit-null mice

PANZANELLI, Patrizia;SASSOE' POGNETTO, Marco;
2006-01-01

Abstract

Mitral cells are the principal neurons of the olfactory bulb. They express high levels of GABAA receptors containing the alpha1 and alpha3 subunits, clustered at reciprocal synapses formed with granule cell dendrites. Here, we investigated whether the specific absence of 1-GABAA receptors in alpha10/0 mice affects GABAergic synapses in mitral cells. We found a marked increase of alpha3 subunit clusters on the cell body of mitral cells of alpha10/0 mice, suggesting that the alpha3 subunit replaces alpha1 in these dendrosomatic synapses. A general increase of alpha3 subunit immunofluorescence was also seen in the external plexiform layer (EPL). However, a quantitative analysis of alpha3 clusters colocalized with gephyrin in the EPL revealed an increase in size, but only a limited increase in density, pointing to partial compensation for the missing alpha1 subunit. Unexpectedly, the number of gephyrin clusters was unchanged, and staining for the alpha2, alpha5, and gamma2 subunits revealed no significant changes in the EPL of alpha10/0 mice. Thus, a fraction of synaptic sites might retain gephyrin while being devoid of GABAA receptors in mutant mice. Despite these changes, the morphology of mitral cells and their postnatal maturation were undistinguishable in wildtype and mutant mice. Ultrastructurally, no difference in morphology of reciprocal synapses was evident between genotypes in the EPL. Gephyrin, as detected by postembedding immunogold labeling, was selectively clustered in GABAergic synapses. However, a strong increase in alpha3 subunit labeling was observed, reflecting the increased cluster size detected in light microscopy. These results indicate that the organization of GABAA receptors is altered in mitral cells of alpha10/0 mice. A single GABAA receptor subtype remains expressed, which partially compensates for the missing 1 subunit, notably in perisomatic reciprocal synapses. In addition, gephyrin clustering appears to be independent of GABAA receptor clustering in a subset of synapses of the mouse EPL.
2006
36th Annual Meeting Society for Neuroscience
Atlanta
14 ottobre 2006
Soc. Neurosci. Abstr
Society for neuroscience
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Panzanelli P; Lagier S; Russo R; Lledo PM; Sassoè-Pognetto M; Fritschy JM
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/39668
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