Deconstructing the Sense of Smell

Coordinators: Maxim Bazhenov, Alex Koulakov, Venkatesh Murthy, Anne-Marie Oswald

Scientific Advisors: Charles Stevens

Olfaction is the final frontier of our senses, one that remains rather mysterious to us. Despite extensive genetic and perceptual data, and a strong push to solve the neural coding problem, fundamental questions about the sense of smell remain unresolved. Unlike in vision and hearing, where relatively straightforward relationships have been established between stimulus features and neural responses, it has been difficult to quantify the properties of odorant molecules that lead to smell percepts. Most natural odors are mixtures of molecules, and there are hundreds of olfactory receptor types in many animals. Therefore, odor codes need to account for the multidimensional relationships between odor features and neural responses, including rich temporal dynamics.

The olfactory system faces daunting challenges: it needs to rapidly detect, identify, categorize, and prepare for memory storage myriad odorants that vary in molecular structure and concentration. Despite this, olfactory processing is achieved by relatively few layers of neurons, with anatomical structures and physiological mechanisms that appear repeatedly in widely divergent species. Thus, a study of olfaction offers the promise of insight into a successful and perhaps optimal biological algorithm for processing complex information. In many animals, the olfactory sense is also used for tracking objects in turbulent environments, an issue that can benefit greatly from physical approaches. In turn, insights gathered here can be used for designing autonomous odor-tracking robots that can help detect threats or other targets. For humans, the sense of smell strongly contributes to our quality of life and is particularly vulnerable to ageing and many neurodegenerative diseases.

This program will address a strong, ongoing need for collaboration between experimental and theoretical neuroscientists to uncover the organizing principles behind olfactory coding and perception. We will bring together scientists from diverse research fields in an attempt to uncover the organizing principles behind the sense of smell. Driven by novel techniques, including next-generation sequencing, optogenetics, and imaging/recordings in awake and behaving animals, there is an explosive growth in experimental data that can newly inform theory. At the same time, a variety of computational and theoretical models have been proposed to explain the data. We believe that the community will deeply benefit from careful collective evaluation and comprehension of the current state of the field. Building on the strong tradition of fruitful collaborative interactions among scientists carrying out theoretical, experimental, and computational research, this KITP program will help to catalyze rapid progress in this field.