Input-dependent gain modulation of neuronal responses and sensorimotor behavior by mid-infrared stimulation

Neuromodulation serves as a cornerstone for brain sciences and clinical applications. Recent research indicates that midinfrared stimulation (MIRS) causes non-thermal modulation of brain functions. Current understanding of its mechanism hampers the routine application of MIRS. In this study, we examined how MIRS with 34.88THz modulated the sensorimotor transformation from neuronal signals to behavior performances in awaking-behaving pigeons. We applied MIRS and electrical stimulation to the pretectal nucleus lentiformis mesencephali (nLM), an essential retinorecipient structure in the pretectum, and compared their effects on the visual-guided eye movement optokinetic nystagmus. We found that MIRS altered eye movements by modulating a specific gain depending on the strength of visual inputs, in a manner different than the effect of ES. Simultaneous extracellular recordings and stimulation showed that MIRS could either excite and inhibit the neuronal activity in the same pretectal neuron depending on its ongoing sensory responsiveness levels in awake-behaving animals. These modulations increased with the size of MIRS output powers. Computational simulations suggest a potential mechanism underlying these effects in which MIRS preferentially enhances the resonance of a carbonyl group of the potassium channel, which critical to the action potential generation, thereby altering neuronal responses to sensory inputs and as a result guiding behavior. Our findings suggest that MIRS could be a promising approach for modulating neuronal functions for brain research and treating neurological diseases.