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Using state-of-the-art computational models to gain insight into the neural basis of smell
Most of food flavor is due to retronasal smell, not when we sniff in but when we breathe out with food in our mouths. This retronasal smell, in fact, is a main determinant of choices for healthy and unhealthy eating. Studying olfactory perception, therefore, will help elucidate the principles of the nervous system on which other sensory perceptions are built. Dr. Gordon Shepherd, Professor of Neurobiology at Yale School of Medicine, uses state-of-the-art computational models based on experimental data to understand the dynamics of odor processing. Building the first full three-dimensional models of neurons and microcircuits, Dr. Shepherd hopes to use the olfactory system as a model to understand how neural circuits as a whole process information.
When we smell the air, odor molecules are represented in the olfactory bulb by spatial patterns as “smell images,” which are processed by neuronal interactions called “microcircuits.” This first step of smelling sharpens the images and passes them to the next stage for higher processing and perception. A pioneer in neuroinformatics who has created an entire database system for neuroscience, Dr. Shepherd hopes to expand his initial model of the olfactory bulb to the next critical stage, the olfactory cortex. Modeling this process should give direct insight into the neural basis of smell perception, and a deeper understanding of how the brain creates the perception of flavor. Currently, there is active research around the world showing that retronasal smell and flavor play a big role in today’s obesity epidemic. A published author of many books, including Neurogastronomy: How the Brain Creates Flavor, and Why It Matters, Dr. Shepherd further hopes to contribute his understanding of olfactory perception to this larger issue of national health and public policy.
Current projects include:
- Microcircuits of the Nervous System: The neural basis of behavior consists of nerve cells and their specific interconnections. Many years ago, Dr. Shepherd suggested in a Scientific American article that nerve cells and their specific connections within a given brain region could be regarded as microcircuits, in analogy with the electronic design of computers. The concept and the term are now widespread, as summarized in the recent Handbook of Brain Microcircuits. Dr. Shepherd’s team uses the olfactory pathway in mammals to analyze the principles of microcircuit organization. For this purpose, his team introduced computational models for deeper insight into experimental results, and his current work has developed a new generation of 3Dl models of the microcircuits in the olfactory bulb, showing how lateral inhibition is critical in carrying out the initial processing of olfactory input. With funding, he will be able to test the hypothesis that olfactory stimuli, represented by odor images in the olfactory bulb, are then converted into distributed memory systems in the olfactory cortex, elucidating this critical step toward small perception.
- Constructing and Navigating the Brain Connectome: To support and integrate his microcircuit work, Dr. Shepherd has constructed a suite of databases called SenseLab, one of the most active database sites for neuroscience. Within SenseLab, NeuronDB archives experimental data and ModelDB archives model data. Dr. Shepherd and his laboratory are further developing these databases to expand their coverage of neurons in NeuronDB and increase neuron and microcircuit models in ModelDB, which are currently over 950. Ultimately, their aim is to establish a national Microconnectome Database (MicroconnectomeDB) that will interface with the national Connectome project, and contribute to a complete database of the brain for both the rodent and the primate in addition to humans.
Bio
Dr. Gordon M. Shepherd grew up in Iowa, and received his B.S. at Iowa State College in 1955, M.D. at Harvard in 1959, and D.Phil. at Oxford in 1962. After postdoctoral training at NIH, MIT, and the Karolinska Institute he joined the faculty at Yale Medical School, where he is Professor of Neurobiology. He introduced the olfactory system as a model for analyzing the properties of neurons and synapses in the brain and the formation of neural images of olfactory molecules. His research has contributed to properties of neuronal dendrites and spines, olfactory processing, and development of the new fields of computational neuroscience, brain microcircuits, neuroinformatics, and neurogastronomy. He has trained over 70 graduate students, postdoctoral fellows and visiting scientists, and published over 280 articles and reviews, with continuous grant support since 1966. His books include The Synaptic Organization of the Brain (5 ed.), Neurobiology (3 ed.), Handbook of Brain Microcircuits, and Neurogastronomy; in the history of neuroscience are Foundations of the Neuron Doctrine, Creating Modern Neuroscience, and Mosso's Circulation of Blood in the Human Brain. He has been chief editor of the Journal of Neurophysiology and Journal of Neuroscience. Visiting positions have included the University of Pennsylvania, College de France, Simon Fraser University, Santa Fe Institute, Ecole Normale Superieure, Institute Pasteur, and Oxford University. He served as a Deputy Provost of Yale University, received honorary degrees from the Universities of Copenhagen and Pavia, and is a member of the American Academy of Arts and Sciences and past president of the Association for Chemoreception Sciences and the Cajal Club.
Dr. Shepherd grew up inspired by the stories of splitting the atom to make the atomic bomb and how it required input from both experimental and theoretical scientists. He has brought this inspiration to bear on revealing the neural basis of olfaction as a pioneer in both the physiology of the olfactory neurons and in computational modeling of these and other neurons. Beyond his scientific work, his medical and physiological training has led him to emphasize the importance of smell as the main component of flavor, and its role in healthy and unhealthy eating, which he emphasizes in his book, Neurogastronomy: How the Brain Creates Flavor, and why it Matters. He has received honorary degrees from the University of Copenhagen and the University of Pavia, and is a member of the American Academy of Arts and Sciences. His main hobbies are building and maintaining his vacation home in Denmark, and supporting his family, who are active in academics, community service, and electronic publishing.