Extrapolating from ∼10% connectivity to ∼2000 total glomeruli in the mouse (Soucy et al., 2009), one can estimate that each PCx neuron connects with ∼200 glomeruli. The number of possible 200-glomerulus combinations CT99021 mouse is >10500, which will be massively undersampled by the PCx population. Correspondingly, PCx firing was reliably triggered by MOB patterns with only 3–4 sites, suggesting cortical cells are not “grandmother” neurons with highly

specific input requirements. Instead, undersampling appears to be balanced by low-stringency coincidence detection requiring activity in a relatively small fraction of connected MOB glomeruli (Apicella et al., 2010 and Franks and Isaacson, 2006). Our results are qualitatively consistent with recent monosynaptic tracing of PCx input (Miyamichi et al., 2011), although we find substantially greater convergence of M/T input. Electrophysiological circuit mapping, besides revealing the functional strength of synaptic contacts, may allow detection of a greater proportion of MOB inputs. Our experiments treat glomeruli as elementary processing units. In vivo imaging supports this assumption for presynaptic OR input (Wachowiak et al., 2004). Postsynaptically, each glomerulus contacts ∼50–75 GABA receptor inhibition M/T neurons (Haberly, 1991), whose activity depends strongly on presynaptic OR input (Tan et al., 2010). However,

all such “sister” M/Ts do not necessarily respond identically (Dhawale et al., 2010, Egaña et al., 2005, Fantana et al., 2008 and Tan et al., 2010). Our data do not address whether sister M/Ts converge onto like cortical targets, although the small size of synaptic inputs suggested this was unlikely. Odor responses of second-order neurons are influenced by lateral interactions between glomeruli in both rat MOB (Fantana et al., 2008) and Drosophila antennal lobe ( Olsen et al., 2007, Olsen and Wilson, 2008 and Shang et al., 2007). While M/T responses were similar Bay 11-7085 for single- and multisite uncaging ( Figure S3), any further decorrelation of odor-evoked firing by local MOB circuits may

facilitate pattern separation by PCx. It also remains to be seen how PCx responses depend on temporal patterning of MOB output ( Bathellier et al., 2008, Cury and Uchida, 2010, Dhawale et al., 2010, Kashiwadani et al., 1999, Schaefer and Margrie, 2007, Spors et al., 2006 and Wesson et al., 2008; see Friedrich et al. [2004] and Perez-Orive et al. [2002] for work in other species). Temporal decoding mechanisms have been described for both individual pyramidal neurons ( Branco et al., 2010) and the PCx network ( Stokes and Isaacson, 2010). While our experiments focused on circuit connectivity, in the future photostimulation may also help evaluate the role of timing in cortical processing. Although glomerular pattern detection in PCx could potentially be explained by a simple linear feedforward mechanism, responses to coactive glomeruli were strongly supralinear.