A novel behavioral paradigm to assess multisensory processing in mice

Justin K. Siemann, Christopher L. Muller, Gary Bamberger, John D. Allison, Jeremy Veenstra-VanderWeele, Mark T. Wallace

Human psychophysical and animal behavioral studies have illustrated the benefits that can be conferred from having information available from multiple senses. Given the central role of multisensory integration for perceptual and cognitive function, it is important to design behavioral paradigms for animal models to provide mechanistic insights into the neural bases of these multisensory processes. Prior studies have focused on large mammals, yet the mouse offers a host of advantages, most importantly the wealth of available genetic manipulations relevant to human disease. To begin to employ this model species for multisensory research it is necessary to first establish and validate a robust behavioral assay for the mouse. Two common mouse strains (C57BL/6J and 129S6/SvEv) were first trained to respond to unisensory (visual and auditory) stimuli separately. Once trained, performance with paired audiovisual stimuli was then examined with a focus on response accuracy and behavioral gain. Stimulus durations varied from 50 ms to 1 s in order to modulate the effectiveness of the stimuli and to determine if the well-established "principle of inverse effectiveness" held in this model. Response accuracy in the multisensory condition was greater than for either unisensory condition for all stimulus durations, with significant gains observed at the 300 ms and 100 ms durations. Main effects of stimulus duration, stimulus modality and a significant interaction between these factors were observed. The greatest behavioral gain was seen for the 100 ms duration condition, with a trend observed that as the stimuli became less effective, larger behavioral gains were observed upon their pairing (i.e., inverse effectiveness). These results are the first to validate the mouse as a species that shows demonstrable behavioral facilitations under multisensory conditions and provides a platform for future mechanistically directed studies to examine the neural bases of multisensory integration.