Effective noninvasive neuronal waveform modulation with sustained and activity-dependent continuous-wave near-infrared laser stimulation

Near-Infrared (NIR) laser is an emerging stimulation technique that has proven its effectiveness as an excitatory stimulus when delivered as high-frequency pulses with potential in future clinical applications. Many studies have focused on the general effect with stationary analyses and not on the spike dynamics and the associated biophysical sources of the modulation.We have explored the effect of continuous-wave (CW)-NIR laser in neurons of Lymnaea stagnalis using sustained and activity-dependent protocols. Sustained illumination has a large potential, but it has been eclipsed by pulsed-laser stimulation, usually claimed to be less invasive. We show how sustained CW-NIR laser illumination safely and effectively modulates the firing rate and neuronal waveform affecting the duration and the spike dynamics, with a minimal effect on amplitude.Using model simulations, we investigated the distinct biophysical candidates behind this effect, finding that no candidate alone was enough to explain the observed phenomena. A temperature model globally affecting the cell biophysics achieved the most accurate reproduction of the observed experimental results, supporting the key role of temperature for the laser modulation.We also present the results using a novel activity-dependent protocol. Controlling a shutter with a real-time software, we detected and predicted the spike generation and assessed its dynamics at distinct stages, e.g., by illuminating the neuron only during depolarization. The analysis highlights the importance of the illumination instant and the relation between thermal dynamics and the observed effect. This protocol can be generalized for clinical interventions as a noninvasive closed-loop CW-NIR stimulation neurotechnology.