GABA receptor heterogeneity modulates dendrodendritic inhibition.

In the olfactory bulb, mitral and tufted cells receive GABAergic inhibition at dendrodendritic synapses with granule cells. Recent studies have revealed a remarkable variability in the subunit composition of GABA(a) receptors in dendrodendritic microcircuits, with differential expression patterns of the alpha1 and alpha3 subunits in different subtypes of mitral and tufted cells. In particular, all mitral cells express the alpha1 subunit, whereas GABA(a)alpha3 is restricted to a subgroup of mitral cells, as well as to several subtypes of tufted cells. To assess the functional relevance of this heterogeneity, we investigated a mouse strain carrying a genetic deletion of the alpha1 subunit. Elimination of GABA(a)alpha1 was partially compensated for in mitral cells by receptors containing the alpha3 subunit, substantially decreasing the frequency of spontaneous inhibitory postsynaptic currents, as well as prolonging their decay time. Evoked inhibition between granule and mitral cells was slower to rise and decay and had smaller amplitude in alpha1 mutants. Remarkably, these changes in synaptic inhibition were accompanied by a significant reduction in the frequency of field oscillations. Therefore, the subunit composition of GABA(a) receptors strongly influences rhythmic activities in the olfactory bulb network. Together, these data indicate that dendrodendritic circuits in the external plexiform layer segregate into parallel pathways involving distinct GABA(a) receptors that are expressed by different subtypes of mitral and tufted cells.