Optogenetic Generation of Neural Firing Patterns with Temporal Shaping of Light Pulses

The fundamental process of information processing and memory formation in the brain is associated with complex neuron firing patterns, which can occur spontaneously or be triggered by sensory inputs. Optogenetics has revolutionized neuroscience by enabling precise manipulation of neuronal activity patterns in specified neural populations using light. However, the light pulses used in optogenetics have been primarily restricted to square waveforms. Here, we present a detailed theoretical analysis of the temporal shaping of light pulses in optogenetic excitation of hippocampal neurons and neocortical fast-spiking interneurons expressed with ultrafast (Chronos), fast (ChR2), and slow (ChRmine) channelrhodopsins. Optogenetic excitation has been studied with light pulses of different temporal shapes that include square, forward-/backward ramps, triangular, left-/right-triangular, Gaussian, left-/right-Gaussian, positive-sinusoidal, and left-/right-positive sinusoidal. Different light shapes result in significantly different photocurrent amplitudes and kinetics, spike-timing, and spontaneous firing rate. For short duration stimulations, left-Gaussian pulse results in larger photocurrent in ChR2 and Chronos than square pulse of the same energy density. Time to peak photocurrent in each opsin is minimum at right-Gaussian pulse. The optimal pulse width to achieve peak photocurrent for non-square pulses is 10 ms for Chronos, and 50 ms for ChR2 and ChRmine. The pulse energy to evoke spike in hippocampal neurons can be minimized on choosing square pulse with Chronos, Gaussian pulse with ChR2, and positive-sinusoidal pulse with ChRmine. The results demonstrate that non-square waveforms generate more naturalistic spiking patterns compared to traditional square pulses. These findings provide valuable insights for the development of new optogenetic strategies to better simulate and manipulate neural activity patterns in the brain, with the potential to improve our understanding of cognitive processes and the treatment of neurological disorders.