In contrast to the projections to amygdala, AON, primary visual cortex and primary somatosensory cortex, projections to piriform cortex lack any apparent spatial organization.
Mitral and tufted cells from a single glomerulus in the olfactory bulb innervate large and very diverse regions of piriform cortex (Figure 2) [27*,28*]. Conversely, piriform neurons receive direct convergent inputs from multiple mitral cells that innervate broadly distributed glomeruli [26*]. The extreme diversity of inputs to piriform cortex is unlikely to develop through known axon guidance mechanisms. Instead, some stochastic target selection process may be used to organize the diverse inputs. Interestingly, excitatory and inhibitory olfactory circuits are wired differently. Compared to layer 2 pyramidal
cells, GABAergic interneurons in layer 1 of piriform cortex receive direct inputs from a significantly
larger number of distributed mitral cells [26*,32]. This convergent connectivity creates layer 1 inhibitory interneurons that are more broadly odor tuned than the excitatory pyramidal neurons [also supported by electrophysiology data, [33*]. Such a configuration is likely to excite only a small number of pyramidal neurons in response to different odors.
Experiments using two-photon calcium imaging and electrophysiology have found sparse odor-evoked neural activity. Typically, only 10% of pyramidal neurons in the piriform cortex respond to a given odor. These neurons are widely distributed in the piriform and lack the spatial organization of the olfactory bulb (Figure 3) [33*,34**]. Even structurally similar odorants appear to activate distinct sets of neurons. Increasing odor concentrations increases the magnitude of responses. However, despite changes in stimulus intensity, odor representations by pyramidal neurons remain sparse [34**]. Odor-selective and distributed neural activity is also observed in the mushroom bodies, a higher order olfactory processing region in the Drosophila brain [35–37].
One function of higher order olfactory processing brain regions may be to generate maximally distinct odor representations. Sparse odor representations in the piriform cortex would encode information that is crucial for the animal to identify and discriminate between related smells. In order to test this hypothesis, responses to complex stimuli such as natural odors of mouse urine and to synthetic odors comprising single or multiple odorants were examined. All of these stimuli activate similar numbers of neurons distributed differently across the piriform cortex [34**]. Thus, complex and mixed odors are not linearly represented by the sum of the responses to the component odorant molecules [33*,34**]. Collectively these data reveal that, unlike other primary sensory circuits, the piriform cortex does
not represent the component features of olfactory stimuli and does not organize the representations topographically.