To internally reflect the sensory environment, animals create neural maps encoding the external stimulus space. From that primary neural code relevant information has to be extracted for accurate navigation. We analyzed how different odor features such as hedonic valence and intensity are functionally integrated in the lateral horn (LH) of the vinegar fly, Drosophila melanogaster. We characterized an olfactory-processing pathway, comprised of inhibitory projection neurons (iPNs) that target the LH exclusively, at morphological, functional and behavioral levels. We demonstrate that iPNs are subdivided into two morphological groups encoding positive hedonic valence or intensity information and conveying these features into separate domains in the LH. Silencing iPNs severely diminished flies' attraction behavior. Moreover, functional imaging disclosed a LH region tuned to repulsive odors comprised exclusively of third-order neurons. We provide evidence for a feature-based map in the LH, and elucidate its role as the center for integrating behaviorally relevant olfactory information.DOI: http://dx.doi.org/10.7554/eLife.04147.001

Responses of olfactory receptors (ORs) can be predicted by applying machine learning methods on a multivariate encoding of an odorant's chemical structure. Physicochemical descriptors that encode features of the molecular graph are a popular choice for such an encoding. Here, we explore the EVA descriptor set, which encodes features derived from the vibrational spectrum of a molecule. We assessed the performance of Support Vector Regression (SVR) and Random Forest Regression (RFR) to predict the gradual response of Drosophila ORs. We compared a 27-dimensional variant of the EVA descriptor against a set of 1467 descriptors provided by the eDragon software package, and against a 32-dimensional subset thereof that has been proposed as the basis for an odor metric consisting of 32 descriptors (HADDAD). The best prediction performance was reproducibly achieved using SVR on the highest-dimensional feature set. The low-dimensional EVA and HADDAD feature sets predicted odor-OR interactions with similar accuracy. Adding charge and polarizability information to the EVA descriptor did not improve the results but rather decreased predictive power. Post-hoc in vivo measurements confirmed these results. Our findings indicate that EVA provides a meaningful low-dimensional representation of odor space, although EVA hardly outperformed "classical" descriptor sets.

Segmentation of functional parts in image series of functional activity is a common problem in neuroscience. Here we apply regularized non-negative matrix factorization (rNMF) to extract glomeruli in intrinsic optical signal (IOS) images of the olfactory bulb. Regularization allows us to incorporate prior knowledge about the spatio-temporal characteristics of glomerular signals. We demonstrate how to identify suitable regularization parameters on a surrogate dataset. With appropriate regularization segmentation by rNMF is more resilient to noise and requires fewer observations than conventional spatial independent component analysis (sICA). We validate our approach in experimental data using anatomical outlines of glomeruli obtained by 2-photon imaging of resting synapto-pHluorin fluorescence. Taken together, we show that rNMF provides a straightforward method for problem tailored source separation that enables reliable automatic segmentation of functional neural images, with particular benefit in situations with low signal-to-noise ratio as in IOS imaging.

Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.

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