Although activating PCx in vivo under our conditions had variable effects on spontaneous M/T cell activity, it consistently reduced M/T cell firing

during odor stimulation. The effects of cortical activation on M/T cell responses were also sensitive to odor concentration, consistent with the notion of a synergistic effect between sensory Epigenetic inhibitor input and cortical activity. The increases and decreases in spontaneous activity across different M/T cells suggests that cortically-evoked disynaptic inhibition is sufficient to suppress spontaneous firing in some M/T cells, while others show a net increase in firing presumably due to IPSP-triggered rebound spikes or “disinhibition” mediated by dSACs. The major effect of cortical activation on M/T cell odor responses was a reduction in odor-evoked excitation and an enhancement of odor-evoked inhibition. The augmentation of purely inhibitory responses further implies that cortical activity amplifies lateral

inhibition during sensory processing in the OB. Although cortical fibers target multiple classes of interneurons in the OB, we suspect that cortically-driven GC excitation plays a dominant role during odor processing. In brain slices, tetanic stimulation of the GC layer (Chen et al., 2000; Halabisky and Strowbridge, 2003) or anterior PCx (Balu et al., 2007) has been shown to facilitate mitral cell-evoked recurrent and lateral inhibition. Thus, cortical excitatory input onto GC proximal dendrites could BMS-907351 datasheet contribute to the relief of the Mg2+ block of NMDARs at distal dendrodendritic synapses and boost or “gate” inhibition onto mitral cells (Balu et al., 2007; Halabisky and Strowbridge, 2003; Strowbridge, 2009). Our in vivo findings that cortical input Rutecarpine preferentially drives OB inhibition during sensory processing are in good agreement with this gating model. However, we do not rule out a contribution of glomerular

layer interneurons to the enhancement of odor-evoked inhibition. While GC-mediated inhibition contributes to odor discrimination (Abraham et al., 2010), the role of lateral inhibition in odor coding is controversial. Although it has been proposed to sharpen the odor tuning of M/T cells belonging to individual glomeruli in a center-surround fashion (Yokoi et al., 1995), this requires a chemotopic map such that glomeruli that respond to similar odorant features are spatially clustered. However, studies have highlighted the lack of a fine scale glomerular chemotopic map and found that M/T cells are not preferentially influenced by nearby glomeruli (Fantana et al., 2008; Soucy et al., 2009). Rather than exerting local actions, lateral inhibition could underlie a more uniform reduction in the activity of M/T cells across all glomeruli and act as a gain control mechanism (Soucy et al., 2009).