Activity in the rat olfactory cortex is correlated with behavioral response to odor: a microPET study

Philippe Litaudon, Caroline Bouillot, Luc Zimmer, Nicolas Costes, Nadine Ravel

How olfactory cortical areas interpret odor maps evoked in the olfactory bulb and translate odor information into behavioral responses is still largely unknown. Indeed, rat olfactory cortices encompass an extensive network located in the ventral part of the brain, thus complicating the use of invasive functional methods. In vivo imaging techniques that were previously developed for brain activation studies in humans have been adapted for use in rodents and facilitate the non-invasive mapping of the whole brain. In this study, we report an initial series of experiments designed to demonstrate that microPET is a powerful tool to investigate the neural processes underlying odor-induced behavioral response in a large-scale olfactory neuronal network. After the intravenous injection of [(18)F]Fluorodeoxyglucose ([(18)F]FDG), awake rats were placed in a ventilated Plexiglas cage for 50 min, where odorants were delivered every 3 min for a 10-s duration in a random order. Individual behavioral responses to odor were classified into categories ranging from 1 (head movements associated with a short sniffing period in response to a few stimulations) to 4 (a strong reaction, including rearing, exploring and sustained sniffing activity, to several stimulations). After [(18)F]FDG uptake, rats were anesthetized to perform a PET scan. This experimental session was repeated 2 weeks later using the same animals without odor stimulation to assess the baseline level of activation in each individual. Two voxel-based statistical analyses (SPM 8) were performed: (1) a two-sample paired t test analysis contrasting baseline versus odor scan and (2) a correlation analysis between voxel FDG activity and behavioral score. As expected, the contrast analysis between baseline and odor session revealed activations in various olfactory cortical areas. Significant increases in glucose metabolism were also observed in other sensory cortical areas involved in whisker movement and in several modules of the cerebellum involved in motor and sensory function. Correlation analysis provided new insight into these results. [(18)F]FDG uptake was correlated with behavioral response in a large part of the anterior piriform cortex and in some lobules of the cerebellum, in agreement with the previous data showing that both piriform cortex and cerebellar activity in humans can be driven by sniffing activity, which was closely related to the high behavioral scores observed in our experiment. The present data demonstrate that microPET imaging offers an original perspective for rat behavioral neuroimaging.