Funded Grants

From percept to molecule: Human olfactory cognition as a key to the neurobiology of olfaction

The rules linking odor perception to odorant structure are unknown. No scientist nor perfumer can predict an odor based on its molecular structure, or decipher a molecular structure based on its smell. It is this puzzle we aim to solve. In vision and audition coding was probed by linking critical physical stimulus dimensions (wavelength/frequency) to patterns of neural activity. But what are the critical physical dimensions in olfaction? Scientists have probed this problem by linking restricted physico-chemical aspects of the stimulus, such as carbon chain-length, to neural activity. However, the olfactory system did not evolve to decode carbon chain-length, but rather to encode the world around us as revealed in olfactory perception. In other words, rather than following the beaten path of probing the system "from molecule to percept" (a phrase used by us and others in countless reviews on olfaction), a more fruitful path may lie in reversing the common approach, and probing the system "from percept to molecule". With this in mind we developed a novel perception-based olfactory space with tangible olfactory axes, based on statistical dimension-reduction of perceptual estimates obtained from human subjects. If the proposed space is valid, it should serve to predict neural activity in the olfactory system. Here we will test the hypothesis that our generated space predicts odorant-induced neural activity in human olfactory epithelium and cortex. Whereas cortical processing will be probed with functional magnetic resonance imaging (fMRI) and implanted electrodes, epithelial processing will be probed with novel methods for measurement from human neurons in vivo. This will include the ground-up effort to develop fibre-optic optical imaging of intrinsic signals from neurons in the human nose. In vision and audition scientists can probe the system within agreed dimensions (color/wavelength; pitch/frequency). Similarly, our proposal generates an olfactory space where one can systematically probe molecular receptor tuning-curves, cellular spatial and temporal coding schemes, as well as higher-order perception. In other words, we propose a common psychophysically-based framework for olfaction research.