Impact of optogenetic pulse design on CA3 learning and replay: A neural model

Optogenetic manipulation of hippocampal circuitry is an important tool for investigating learning in vivo. Numerous approaches to pulse design have been employed to elicit desirable circuit and behavioral outcomes. Here, we systematically test the outcome of different single-pulse waveforms in a rate-based model of hippocampal memory function at the level of mnemonic replay extension and de novo synaptic weight formation in CA3 and CA1. Lower-power waveforms with long forward or forward and backward ramps yield more natural sequence replay dynamics and induce synaptic plasticity that allows for more natural memory replay timing, in contrast to square or backward ramps. These differences between waveform shape and amplitude are preserved with the addition of noise in membrane potential, light scattering, and protein expression, improving the potential validity of predictions for in vivo work. These results inform future optogenetic experimental design choices in the field of learning and memory.