Infrared neural stimulation (INS) is a promising area of interest for the clinical application of a neuromodulation method. This is in part because of its low invasiveness, whereby INS modulates the activity of neural tissue mainly through temperature changes. Additionally, INS may provide localized brain stimulation with less tissue damage. The inferior colliculus (IC) is a crucial auditory relay nuclei, and a potential target for clinical application of INS to treat auditory diseases and develop artificial hearing devices. Here, using continuous INS with low to high power density, we demonstrate laminar modulation of neural activity in the mouse IC in the presence and absence of sound. We investigated stimulation parameters of INS to effectively modulate neural activity in a facilitatory or inhibitory manner. A mathematical model of INS-driven brain tissue was first simulated, temperature distributions were numerically estimated, and stimulus parameters were selected from the simulation results. Subsequently, INS was administered to the IC of anesthetized mice, and the modulation effect on neural activity was measured using an electrophysiological approach. We found that the modulatory effect of INS on spontaneous neural activity was bidirectional between facilitatory and inhibitory effects. The modulatory effect on sound-evoked responses produced only an inhibitory effect to all examined stimulus intensities. Thus, this study provides important physiological evidence on the response properties of IC neurons to INS. Overall, INS can be used for the development of new therapies for neurological diseases and functional support devices for auditory central processing.Significance statementUsing continuous infrared neural stimulation (INS) of low to high power density, we sought to examine laminar modulation of neural activity in the mouse inferior colliculus (IC) in the presence and absence of sound. We found that the modulatory effect of INS on spontaneous neural activity was bidirectional between facilitatory and inhibitory effects. Additionally, the modulatory effect on sound-evoked responses produced only an inhibitory effect at all examined stimulus intensities. Thus, this study provides important physiological evidence on the response properties of IC neurons to INS. Moreover, INS can be used for the development of new therapies for neurological diseases and functional support devices for auditory central processing.