A method for the rapid automated assessment of olfactory function

We have developed a strategy for the rapid high-throughput screening of odor responsivity in genetically altered mice (in fact, any experimentally altered animal). Specifically, the report presents the development and validation of a fully automated procedure based on the evaluation of an animal's stimulus-induced reflexive breathing response (i.e. sniffing behavior) to both air and odorant stimuli. The method requires no training of the animal to be screened and the outcome of the evaluation yields an operationally defined measure. Briefly, using whole-body plethysmography, the procedure determines the numerical values for a set of 14 respiratory measures in response to the presentation of air and a well-above-threshold concentration of the odorant propanol. These measures of stimulus-induced sniffing are incorporated into a model that defines a single univariate measure of response behavior, or 'Sniffing Index', for each screened animal. The approach significantly discriminated between the reflexive sniffing response of a control group of mice and that of an experimentally defined manipulated group for which, a priori, we expected to observe a robust altered breathing response to odorant stimulation (i.e. non-odor-aversion-conditioned versus odor-aversion-conditioned C57BL/6J mice). Further, the procedure was able to significantly discriminate between a mutant phenotype with documented alterations in physiologic and behavioral function (namely, the OMP-null mutant), and their background strain. In addition, applying epidemiologic screening principles to the observed data, we established an operational procedure for the evaluation of unknown animals.