Synaptic inhibition in the olfactory bulb accelerates odor discrimination in mice.

The ability to distinguish between similar odors is essential to making sense of the olfactory world. Although local inhibitory circuits have been recognized as conducive to spatiotemporal pattern separation, causal evidence linking the two has been lacking. In an elegant study, Abraham and colleagues provide a direct link between local synaptic inhibition in the main olfactory bulb and odor-discrimination performance, and show that local inhibition may represent a neuronal mechanism of pattern separation.

To assess the contribution of local inhibition to odor discrimination, the authors employ a clever combination of strategies to bi-directionally modulate recurrent inhibition of mitral cells. To increase recurrent inhibition of mitral cells, the authors reasoned that ablation of the GluA2 subunit in granule cells should increase calcium influx into these neurons and, consequently, enhance gamma-aminobutyric acid (GABA) release at granule cell-mitral cell dendrodendritic synapses. Using a lentiviral Cre-based approach, the authors show that ablation of the GluA2 subunit in approximately 40-50% of granule cells resulted in increased recurrent inhibition of mitral cells both in vitro and in vivo. Importantly, mice with increased recurrent inhibition of mitral cells showed faster discrimination between similar odors than controls. In a complementary series of experiments, the authors showed that ablation of the GluN1/NR1 subunit in granule cells decreased recurrent inhibition onto mitral cells and slowed down discrimination time of similar odors. Interestingly (and perhaps expectedly), changes in recurrent inhibition on mitral cells did not impact an animal’s ability to distinguish between dissimilar odors or olfactory memory. Together, these gain- and loss-of-function experiments directly implicate local inhibition as a potential neuronal mechanism of pattern separation in the olfactory bulb and suggest that local inhibition may subserve a similar role in other brain regions where pattern separation occurs.

These elegant studies help resolve the question of the function of local inhibition in the mammalian olfactory bulb (OB), greatly expanding our understanding of sensory processing mechanisms.

In contrast to most brain regions, inhibitory interneurons far outnumber excitatory neurons in the OB.
However, the function of bulbar inhibition has remained unclear because it is difficult to obtain electrophysiological recordings from the small granule cells (GCs), the major source of inhibition in the glomeruli of the OB.
In this study, the authors take advantage of a spatiotemporally localized gene deletion to determine the function of local inhibition in the OB.
They selectively deleted glutamatergic inputs onto the GCs to alter GC inhibition in the OB.
Remarkably, these bidirectional perturbations led to corresponding changes in the speed of discrimination between odors with subtle differences.
Deletion of the GluA2 subunit results in increased Ca2+ influx into GCs, increased inhibition by GCs and faster discrimination between similar odors.
In contrast, deletion of the GluN1 subunit results in decreased Ca2+ influx, decreased inhibition by GCs and slower discrimination between similar odors. The authors speculate that odors with subtle differences might produce overlapping activity patterns that are spatiotemporally complex and overlapping, and thus require rapid refinement by granule cell-mediated inhibition in the OB.
This study uses a powerful targeted approach to dissect the functions of local inhibition in olfactory processing in the OB.