Event Abstract Back to Event Synaptic Inhibition in the Olfactory Bulb Controls Odor Discrimination Time in Mice Nixon M. Abraham1, 2*, Derya R. Shimshek3, Rolf Sprengel3, Peter H. Seeburg3, Matthias Klugmann4, 5, Troy W. Margrie6, Andreas T. Schaefer1, 6 and Thomas Kuner1, 2 1 Max Planck Institute for Medical Research, WIN Olfactory Dynamics Group, Germany 2 University of Heidelberg, Institute of Anatomy and Cell Biology, Germany 3 Max-Planck-Institute for Medical Research, Department of Molecular Neurobiology, Germany 4 University of Auckland, Department of Molecular Medicine and Pathology, New Zealand 5 University of Mainz, Department of Physiological Chemistry, Germany 6 University College London, The Department of Neuroscience, Physiology and Pharmacology, United Kingdom In the olfactory bulb (OB), the reciprocal dendro-dendritic synapse, connecting mitral (M) /tufted (T) cells and granule cells (GC), mediates reciprocal and lateral inhibition, mechanisms that may contribute to temporal processing and contrast enhancement during odor discrimination. To examine the role of glutamate receptors at the reciprocal synapse, the function of AMPA and NMDA receptors of GCs was specifically perturbed. Spatio-temporally controlled deletions of the GluR-B and NR1 subunits in the GC of the OB was achieved by stereotaxic delivery of adeno associated virus (AAV1/2) expressing the Cre recombinase in mice carrying gene targeted loxP-flanked GluR-B or NR1 alleles. The behavioral consequences of OB specific GluR deletions were assessed by determining the odor discrimination time (DT) using go-no go operant conditioning paradigm [1]. DTs were determined for dissimilar (simple odors) and highly similar odors (binary mixtures). AAV-mediated Cre expression in the OB of mice with floxed GluR-B alleles resulted in GluR-B deletion in about 40% of the GC population. The DTs were reduced for similar odors while they remained unchanged for dissimilar odors. The same perturbation also caused increased recurrent inhibition of mitral cells in OB slices. Cre expression in mice with floxed NR1 alleles resulted in deletion of NR1 in about 45% of the GC population. In these mice the DTs were increased for similar odors and remained unchanged for dissimilar odors. This modification also caused decreased recurrent inhibition of mitral cells in OB slices. Hence, deleting the GluR-B subunit caused increased inhibition and possibly better contrast enhancement, thereby allowing faster odor discrimination of similar stimuli whereas deleting the NR1 subunit caused the opposite effect. In summary, these results show that inhibitory interactions between M/T cells and GC play an essential role in the refinement of the odor stimuli and that processing time differences are mainly generated in the OB.