Precision Induction and Distinction of Coughing and Sneezing Reflexes in Mice

Coughing and sneezing, as vital respiratory defensive reflexes, have seen research into their mechanisms constrained by the nonspecific stimulation inherent in traditional models. Existing methods, such as capsaicin or citric acid nebulization, can simultaneously activate coughing (mediated by tracheal C fibers) and sneezing (mediated by nasal trigeminal nerves), leading to confounded behavioral observations. Although previous studies have attempted to distinguish coughing and sneezing by analyzing respiratory patterns or acoustic signatures, these studies lack models that can specifically stimulate the trachea and nasal cavity. Here, we developed a murine model employing site-specific stimulation of the trachea (to induce cough) and nasal cavity (to trigger sneeze). Using synchronized multimodal recordings, whole-body plethysmography (WBP), wideband ultrasonic microphones (0-250 kHz), and high-speed videography (160 fps), we quantified distinct physiological signatures of cough and sneeze. Our findings revealed that both coughing and sneezing exhibit single- and double-peak respiratory patterns, with significant differences in their audio frequency spectra composition. By constructing a coordinate system based on audio features, we were able to effectively distinguish coughing and sneezing, mapping them to different quadrants of the coordinate axis. This study, through anatomically specific stimulation and acoustic feature analysis, established a mouse model capable of quantitatively distinguishing between coughing and sneezing, providing a high-precision experimental method for the investigation of airway defense reflexes and targeted therapeutic development.