Persistent Light-Induced Reduction of Neuronal Excitability: Implications for Non-Optogenetic control of Brain Actvity

The primary objective of this study was to determine whether light stimulation can induce a persistent reduction in neuronal activity within the central nervous system. Using repeated pulses of blue light (5 seconds, {lambda} = 430 - 495nm at 19 mW, [~]2.4 mW/mm{superscript 2}) on cortical slices, we observed a robust and sustained decrease in evoked firing activity, approximately 60% relative to baseline, in cortical neurons from both male and female mice. This inhibitory effect persisted for more than twenty minutes following stimulation. In human cortical slices, the effect was more variable. While some neurons showed reduced activity, others, particularly those from female subjects, exhibited increased firing in response to light. The long-lasting modulation of neuronal excitability appears to result from changes in both the passive (membrane resistance and resting potential) and active (voltage-dependent Na and K channels) properties of neurons. These findings suggest that light stimulation within the visible spectrum may serve as a tool to treat brain pathologies produced by neuronal hyperexcitability. We propose a roadmap for further research, including in vivo validation, exploration of stimulation parameters, and evaluation in pathological models. Importantly, the infrastructure and protocols developed for optogenetic studies provide immediate opportunities to test the therapeutic potential of light alone, without requiring exogenous opsin expression.