Opening these black boxes has been difficult. To do so would require estimates of activity in many—ideally, all—neurons carrying perceptually relevant signals. Because sensory representations tend to be distributed over large numbers of neurons, such estimates have generally remained elusive (see Kreher et al. [2008] for a notable exception). Here, we take advantage of the well-characterized olfactory system

of fruit flies to relate knowledge of the population representations of odors to behavioral measures of odor discrimination. Flies detect odorous molecules with arrays of ∼50 types of olfactory receptor neuron (ORN) (Couto et al., 2005 and Fishilevich and Vosshall, 2005) whose response spectra are determined by the expression of a single functional odorant receptor (Clyne et al., 1999, Vosshall et al., Topoisomerase inhibitor 1999, Dobritsa et al., 2003 and Hallem et al., 2004). The mean spike rates evoked by 110 odorants in 24 of the ∼50 ORN types of adult flies have been measured (Hallem and Carlson, 2006 and Hallem et al., 2004), providing LDN-193189 concentration a quantitative description of activity in approximately half of the neuronal population at the input stage of the olfactory system. ORN axons segregate by receptor type (Gao et al., 2000 and Vosshall et al., 2000) and transmit signals via separate

synaptic relays, the glomeruli of the antennal lobe, to discrete classes of excitatory projection neurons (ePNs) (Jefferis et al., 2001 and Stocker Mephenoxalone et al., 1990). ePN responses are saturating functions of input from cognate ORNs that scale inversely with total ORN activity (Olsen et al., 2010). Thus, a two-parameter transformation incorporating direct and total ORN activity allows estimation of mean ePN spike rates from measured ORN spike rates. ePNs project to two brain areas: the mushroom

body (MB) and the lateral horn (LH) of the protocerebrum. Innate odor-driven behaviors are thought to rely on circuits of the LH only (Heimbeck et al., 2001), whereas learned behaviors require the MBs (Heisenberg et al., 1985), whose plastic output synapses are the postulated storage sites of learned associations (Heisenberg, 2003). The MBs only receive feedforward excitation from cholinergic ePNs, whereas the LH receives parallel excitatory and inhibitory inputs via ePNs and a functionally uncharacterized group of mostly multiglomerular GABAergic inhibitory PNs (iPNs) (Jefferis et al., 2001, Lai et al., 2008, Okada et al., 2009 and Tanaka et al., 2012). Inhibition has been invoked in many sensory systems as a mechanism for enhancing contrast (Barlow, 1953, Hartline et al., 1956 and Kuffler, 1953), exerting gain control (Barlow, 1961, Olsen et al., 2010, Olsen and Wilson, 2008 and Root et al., 2008), or binding neurons representing different stimulus features in synchrony (Gray et al., 1989, Laurent and Davidowitz, 1994 and Stopfer et al., 1997). It is currently unknown whether iPNs play any of these roles.