Using the olfactory system as a model that spans multiple levels of space, time and disciplines, his studies ranged from molecular to behavioral, recognized by an annual lecture at Yale University on "integrative neuroscience".
[4] New concepts to replace the classical "neuron doctrine" were hypothesized, and the term "microcircuit" was introduced for characterizing specific patterns of synaptic interactions in the nervous system.
The lab has introduced viral tracing methods to reveal widely dispersed clusters of granule cells which are hypothesized to be necessary for processing the distributed glomeruli activated by odor stimuli.
These experimental data were used to build novel 3D computational models of the distributed mitral and granule cell circuits, to obtain insight into the nature of the processing that underlies smell perception.
[6] A new appreciation of the human sense of smell suggested a new focus on retronasal smell, which activates an extensive "flavor system" in the human brain; this led in 2015 to a new field of "neurogastronomy", based on his book of that name[7] which has among its goals enhancing understanding of the factors contributing to clinical conditions and global health.
A new society and annual meeting have been formed by Shepherd, Dan Han, Frédéric Morin, Charles Spence, Tim McClintock, Bob Perry, Jehangir Mehta, Kelsey Rahenkamp, Siddharth Kapoor, Ouita Michel, and Bret Smith, called the International Society of Neurogastronomy (ISN).
Current studies with paleontologist Timothy Rowe suggest that during evolution this basic three layer microcircuit combined with reptilian dorsal cortex to form the neocortex.