Surgical preparation of mice for recording cardiorespiratory parameters in vivo

•Mice are maintained under anaesthesia and ventilated for more than 6h.•This method enables multiple nerve recordings.•Our approach enables complex physiological studies to be conducted in vivo in mice. The explosion in the use of genetically modified mouse strains to investigate function in biology has an enormous potential to expand on pharmacological studies traditionally conducted in rats. A key limitation to date is the inability to record from multiple nerves in an anaesthetised mouse for long periods. Here we describe an in vivo preparation that maintains mice in a suitable physiological state, under anaesthesia, for at least 6hr and also enables multiple cardiorespiratory recordings over that time. Using the method described, blood pressure, heart rate, phrenic nerve activity, splanchnic nerve activity and heart rate were able to be recorded for hours in an anaesthetised, paralysed and mechanically ventilated mouse. Existing anaesthetised mouse preparations are limited by difficulties in maintaining mice under anaesthesia for long periods. This time constraint therefore limits the surgical time and number of cardiorespiratory variables recorded. It also limits the type of stimuli that can be administered and the length of recorded responses. The method described here optimises these variables to overcome these challenges. In summary, we report an approach that enables physiological and pharmacological studies previously undertaken in larger animals or ‘reduced’ preparations, to be conducted in vivo in mice. We anticipate that the use of this preparation will enable a deeper understanding of genetic variation, and allow a much greater level of phenotypic characterisation in genetically modified mice.