Thus, despite receiving substantial excitatory input from receptor neurons, the MCs have a very small response (defined here as the change in the MC firing rate with respect to spontaneous baseline activity). The reduction in the response is due to the strong inhibition provided by the GC. These inhibitory inputs almost completely cancel the excitation provided Fludarabine clinical trial by the receptor neurons (see “The State Dependence of the MC Code” in Experimental Procedures for a more quantitative analysis). The

balance between excitation and inhibition has implications for olfactory code carried by the MCs. For the MCs that receive inhibitory inputs from the GC, the odorant responses are substantially reduced. If all MCs receive these inhibitory inputs, only weak (i.e.,

undetectable) activity that is necessary to drive GC above the firing threshold remains (Figure 2B). Because the inputs to all of the MCs are substantially balanced by inhibition and none of the MCs displays strong odorant responses in this case, we call this complete combinatorial compensation. On the other hand, as shown in Figure 2C, the responses of a subset of MCs may accurately reproduce the inputs that they receive from the receptor neurons. This is because these cells do not receive the compensating inhibition from the GC, which is therefore incomplete. Inhibitory inputs from GCs selectively reduce the responses of some MCs, while leaving other MCs responsive. The Selleck Rucaparib sustained combinatorial representation carried by MCs becomes sparse. Therefore, our model can yield sparse sustained MC responses observed experimentally (Rinberg et al., 2006). Sparsening of the responses of MCs reduces redundancy in the representation of odorants (Figure 3A). The role of GCs in this case is to remove overlaps between combinatorial receptor inputs. The removal of overlaps makes MC activation patterns Thiamine-diphosphate kinase more independent for different odorants. Redundancy reduction may occur in a task-dependent manner. This means that the particular overlap that is removed depends on the activation of the centrifugal cortico-bulbar projections (Figure 3A versus

Figure 3B). By activating/deactivating the particular subsets of GCs, these projections may change the MC code to better discriminate the set of odorants relevant to specific behavior. Figure 2A illustrates the regime when GCs are never or rarely active. The MC code in this case is dense and reflects glomerular inputs. Activation of GCs, as shown in Figure 2B, leads to sparse odorant representations. Because the transition between full and sparse codes occurs upon transition between anesthetized and awake states, we suggest that Figures 2A and 2B illustrate these two regimes of the bulbar network. The prediction of this model is therefore that GCs are less active in anesthetized animals than in awake and behaving animals. We now consider the case of several GCs.