fMRI study of olfactory processing in mice under three anesthesia protocols: Insight into the effect of ketamine on olfactory processing

Functional magnetic resonance imaging (fMRI) is a valuable tool for studying neural activations in the central nervous system of animals due to its wide spatial coverage and non-invasive nature. However, the advantages of fMRI have not been fully realized in functional studies in mice, especially in the olfactory system, possibly due to the lack of suitable anesthesia protocols with spontaneous breathing. Since mice are widely used in biomedical research, it is desirable to evaluate different anesthesia protocols for olfactory fMRI studies in mice. Dexmedetomidine (DEX) as a sedative/anesthetic has been introduced to fMRI studies in mice, but it has a limited anesthesia duration. To extend the anesthesia duration, DEX has been combined with a low dose of isoflurane (ISO) or ketamine (KET) in previous functional studies in mice. In this report, olfactory fMRI studies were performed under three anesthesia protocols (DEX alone, DEX/ISO, and DEX/KET) in three different groups of mice. Isoamyl-acetate was used as an odorant, and the odorant-induced neural activations were measured by blood oxygenation-level dependent (BOLD) fMRI. BOLD fMRI responses were observed in the olfactory bulb (OB), anterior olfactory nuclei (AON), and piriform cortex (Pir). Interestingly, BOLD fMRI activations were also observed in the prefrontal cortical region (PFC), which are most likely caused by the draining vein effect. The response in the OB showed no adaptation to either repeated odor stimulations or continuous odor exposure, but the response in the Pir showed adaptation during the continuous odor exposure. The data also shows that ISO suppresses the olfactory response in the OB and AON, while KET enhances the olfactory response in the Pir. Thus, DEX/KET should be an attractive anesthesia for olfactory fMRI in mice.