Scherbarth, and R. Singer for technical buy Venetoclax assistance, and R. Singer, G. Shoeman, and A. Schoell for fish care. We are grateful to S. Higashijima for sharing the vglut2a:DsRed line. This work was supported by the Max Planck Society and the Deutsche Forschungsgemeinschaft (J.H.B., BO3746/1-1). J.H.B. and S.R. are members of the Interdisciplinary Centre for Neurosciences (IZN) and the Excellence Cluster “CellNetworks” at Heidelberg University. C.M.M. is recipient of a “Nachwuchsförderungskredit”

of Universität Zürich. “
“Cortical regions underlying vision, audition, and somatosensation receive sensory information from the thalamus and also make corticothalamic feedback projections that influence thalamic sensory processing (Briggs and Usrey, 2008; Cudeiro

and Sillito, 2006). Thus, the cortex has the fundamental capacity to modulate the nature of its own input. In contrast to other sensory modalities, the olfactory system is unusual in that sensory information is initially processed in the olfactory bulb (OB) and conveyed directly (without a thalamic relay) to the olfactory cortex. Like the corticothalamic pathway, anatomical studies show that the axons of olfactory cortex pyramidal cells selleck inhibitor send abundant, long-range “centrifugal” projections back to the OB (de Olmos et al., 1978; Haberly and Price, 1978; Luskin and Price, 1983; Shipley and Adamek, 1984). However, functional properties of cortical feedback projections such as their neuronal targets, effects on local circuits, and impact on OB odor processing in vivo are poorly understood. In the OB, principal mitral and tufted (M/T) cells belonging to unique glomeruli are activated by particular molecular features of individual odorants (Rubin and Katz, 1999; Soucy et al., 2009; Uchida et al., 2000). M/T cell output is strongly regulated by local GABAergic interneurons (Shepherd

et al., 2004). Indeed, odors can elicit purely inhibitory M/T cell responses reflecting a major role for circuits mediating lateral inhibition in the OB (Cang and Isaacson, 2003; Davison and Katz, 2007; Yokoi et al., 1995). Reciprocal dendrodendritic synapses between M/T cell lateral dendrites and the Adenylyl cyclase distal dendritic spines of GABAergic granule cells (GCs) are the major source of recurrent and lateral inhibition of M/T cells and dendrodendritic inhibition triggered by M/T cell glutamate release is strongly dependent on the activation of GC NMDA receptors (NMDARs) (Chen et al., 2000; Isaacson and Strowbridge, 1998; Schoppa et al., 1998). Sensory information from the OB is relayed via M/T cell axons within the lateral olfactory tract (LOT) directly to pyramidal cells in piriform cortex (PCx), a three-layered cortical region where bulbar inputs are integrated to form odor percepts (Haberly, 2001).