In mice, each olfactory sensory neuron (OSN) expresses only one OR gene out of the repertoire of over 1000, and OSNs expressing a common OR send convergent axonal projections to roughly 2 glomeruli in the MOB (Buck and Axel, 1991 and Mombaerts et al., 1996). Each glomerulus is associated with a subset of 25–50 mitral/tufted cells, which receive primary excitatory input from isofunctional OSNs and respond selectively to the odor ligands of their related OR (Tan et al., 2010).

An individual odorant evokes a stereotypical spatial activation pattern at the glomerular layer in the MOB (Rubin and Katz, 1999), which is then transmitted to the piriform cortex through the axons of mitral/tufted cells via the lateral olfactory tract (LOT). Surprisingly, individual odorants evoke sparsely and randomly distributed sets of neurons in the piriform cortex (Stettler Tofacitinib order and Axel, 2009). The abrupt randomization of cortical activation patterns might be generated by divergent projections buy Ku-0059436 from the bulb to the cortex and/or associative connections within the cortex. Recent tracing studies reveal that the axonal terminals of individual mitral/tufted

cells are diffusively distributed throughout the piriform cortex (Ghosh et al., 2011 and Sosulski et al., 2011). Transsynaptic tracing and intracellular recordings show that individual pyramidal neurons (PNs) in the piriform integrate inputs from at least scores of glomeruli (Davison and Ehlers, 2011 and Miyamichi et al., 2011). In addition to bulbar inputs, PNs in the olfactory cortical areas are believed to receive extensive recurrent intracortical connections (Haberly, 2001). However, the exact nature and physiological importance of intracortical associative connections

have not been clearly established in the olfactory system. In this issue of Neuron, two elegant studies provide direct evidence for the presence and functional roles of long-range cortical either excitation in the piriform cortex ( Franks et al., 2011 and Poo and Isaacson, 2011). In the Franks et al. study, the authors used optogenetics to dissect intracortical connections in brain slices (Franks et al., 2011). By delivering genes with viral vectors, the authors expressed the light-sensitive channel Channelrhodopsin-2 in a focal cluster of neurons in the mouse anterior piriform cortex. These ChR2+ neurons were activated by brief light pulses and their effects were examined by whole-cell recordings from ChR2− PNs at different distances from the center of viral infection. In a vast majority of recorded cells, light stimulations evoked large monosynaptic excitatory postsynaptic currents (EPSCs).