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Theoretical analysis of low-power fast optogenetic control of firing of Chronos-expressing neurons

Abstract. A detailed theoretical analysis of low-power, fast optogenetic control of firing of Chronos-expressing neurons has been presented. A three-state model for the Chronos photocycle has been formulated and incorporated in a fast-spiking interneuron circuit model. The effect of excitation wavelength, pulse irradiance, pulse width, and pulse frequency has been studied in detail and compared with ChR2. Theoretical simulations are in excellent agreement with recently reported experimental results and bring out additional interesting features. At very low irradiances (0.005  mW  /  mm2), the plateau current in Chronos exhibits a maximum. At 0.05  mW  /  mm2, the plateau current is 2 orders of magnitude smaller and saturates at longer pulse widths (∼700  ms) compared to ChR2 (∼350  ms). Ipeak in Chronos saturates at much shorter pulse widths (1775 pA at 1.5 ms and 5  mW  /  mm2) than in ChR2. Spiking fidelity is also higher at lower irradiances and longer pulse widths compared to ChR2. Chronos exhibits an average maximal driven rate of over 200  spikes  /  s in response to 100  pulses  /  s stimuli, each of 1-ms pulse-width, in the intensity range 0 to 200  mW  /  mm2. The analysis is important to not only understand the photodynamics of Chronos and Chronos-expressing neurons but also to design opsins with optimized properties and perform precision experiments with required spatiotemporal resolution.