Vasopressin receptor 1a, oxytocin receptor, and oxytocin knockout male and female mice display normal perceptual abilities towards non-social odorants.

Genetic knockouts of the vasopressin receptor 1a (Avpr1a), oxytocin receptor (Oxtr), or oxytocin (Oxt) gene in mice have helped cement the causal relationship between these neuropeptide systems and various social behaviors (e.g., social investigation, recognition, and communication, as well as territoriality and aggression). In mice, these social behaviors depend upon the olfactory system. Thus, it is critical to assess the olfactory capabilities of these knockout models to accurately interpret the observed differences in social behavior. Prior studies utilizing these transgenic mice have sought to test for baseline deficits in olfactory processing; predominantly through use of odor habituation/dishabituation tasks, buried food tests, or investigation assays using non-social odorants. While informative, these assays rely on the animal's intrinsic motivation and locomotor behavior to measure olfactory capabilities and thus, often yield mixed results. Instead, psychophysical analyses using operant conditioning procedures and flow-dilution olfactometry are ideally suited to precisely quantify olfactory perception. In the present study, we used these methods to assess the main olfactory capabilities of adult male and female Avpr1a, Oxtr, and Oxt transgenic mice to volatile non-social odorants. Our results indicate that homozygous and heterozygous knockout mice of all three strains have the same sensitivity and discrimination ability as their wild-type littermates. These data strongly support the hypothesis that the observed social deficits of these global knockout mice are not due to baseline deficits of their main olfactory system.

Protocol for quantifying the odor detection threshold of mice.

Perceptual measures of odor threshold provide a mechanism to compare sensitivity across species and to gauge stimulus concentrations for functional experiments. Here, we present a protocol to precisely quantify the odor detection threshold of mice. We describe the construction of a head-fixed operant conditioning behavioral rig and provide details of the training and testing procedures. This approach can be used to compare the sensitivity of mice across odorants and to quantify detection differences associated with genetic mutations or pharmacological manipulations. For complete details on the use and execution of this protocol, please refer to Johnson et al. (2023),1 Jennings et al. (2022),2 Williams and Dewan (2020),3 and Dewan et al. (2018).4.