Cell- and layer-type specific intracortical effects of pulsed and continuous wave infrared neural stimulation revealed by high-density laminar recordings in the rat neocortex

Infrared (IR) neuromodulation research over the past decade has consistently shown that temperature is an important neural state variable. Several studies have described the ability to stimulate or block peripheral nerve activity with IR radiation. The promise of IR inhibition in the treatment of neurodegenerative diseases such as epilepsy underscores the importance of further elucidating its biophysical mechanism. In this study, the effects of IR neuromodulation on cortical neurons in vivo were investigated using high-density laminar recordings. The neocortex of anesthetized rats was exposed to pulsed and continuous wave (CW) infrared light (1550 nm) using a photonic microtool. Over 7500 single units were recorded from 8 rats using a Neuropixels probe. Single units from the cortex were identified as putative principal neurons and inhibitory interneurons with suppressed or increased activity, highlighting cell- and layer-specific responses. We analyzed the temporal dynamics during stimulation trials and their correlation with temperature changes. Pulsed light preferentially excited units over suppression, whereas CW light tended to suppress. Temperature increases varied with frequency and were correlated with the number of responsive units. Examining changes in the baseline firing rate across trials indicated a long-lasting effect of stimulation, maintaining the excitability of the affected neurons at elevated levels. Furthermore, analysis of individual neuron responses at varying frequencies revealed diverse patterns. This study provides new insights into the mechanisms of infrared neuromodulation by accurately characterizing layer- and cell-type-specific responses. By analyzing thousands of neurons, our findings on neuronal sensitivity to infrared irradiation parameters may help optimize future applications.