Characterizing optogenetically mediated rebound effects in anaesthetized mouse primary visual cortex.

Optogenetic tools have been used to investigate neural circuits in mouse primary visual cortex (V1), where channelrhodopsin-mediated activation (photostimulation) of inhibitory interneuron subtypes expressing parvalbumin (Pvalb+), somatostatin (SOM+) or vasoactive intestinal peptide (VIP+) can alter the responses of excitatory pyramidal neurons. Some studies have mentioned rebound spiking after this photostimulation, but no systematic analysis of these post-inhibitory rebound effects has yet been performed. Here, we characterized optogenetically mediated rebound effects in pyramidal cells and interneurons following Pvalb+, SOM+ or VIP+ photostimulation in isoflurane anaesthetized mice and investigated whether V1 network features such as activity and connectivity can affect rebound magnitude. We found converging evidence that rebounds were largest when interneuron photostimulation was coupled with visual stimuli that strongly activate V1. Many directly photostimulated interneurons showed post-activation effects that differed from rebounds in polarity and timing. Finally, Pvalb+ photostimulation produced the largest rebounds. Our findings suggest that both cellular and network mechanisms contribute to rebound effects in mouse V1. KEY POINTS: To study cortical circuits, light-activated optogenetic proteins targeted to inhibitory interneurons are used to suppress excitatory pyramidal cells, but after the light is turned off pyramidal cells sometimes show excess spiking, which is called a post-inhibitory rebound. We investigated whether optogenetically mediated post-inhibitory rebounds are affected by local cortical network activity and connectivity in anaesthetized mouse visual cortex. We show that visual stimuli that strongly activate visual cortex increase the magnitude of both post-inhibitory rebounds in pyramidal cells and novel post-excitation effects in the directly optogenetically activated interneurons. Activating different interneuron subtypes, each with distinct connection patterns within the local network, elicits different rebound effects. The properties of optogenetically mediated rebound effects in cortex can provide insights into how excitation and inhibition are regulated during normal brain function.