Brief wide-field photostimuli evoke and modulate oscillatory\n reverberating activity in cortical networks

Cell assemblies manipulation by optogenetics is pivotal to advance\nneuroscience and neuroengineering. In in vivo applications, photostimulation\noften broadly addresses a population of cells simultaneously, leading to\nfeed-forward and to reverberating responses in recurrent microcircuits. The\nformer arise from direct activation of targets downstream, and are\nstraightforward to interpret. The latter are consequence of feedback\nconnectivity and may reflect a variety of time-scales and complex dynamical\nproperties. We investigated wide-field photostimulation in cortical networks in\nvitro, employing substrate-integrated microelectrode arrays and long-term\ncultured neuronal networks. We characterized the effect of brief light pulses,\nwhile restricting the expression of channelrhodopsin to principal neurons. We\nevoked robust reverberating responses, oscillating in the physiological gamma\nfrequency range, and found that such a frequency could be reliably manipulated\nvarying the light pulse duration, not its intensity. By pharmacology,\nmathematical modelling, and intracellular recordings, we conclude that gamma\noscillations likely emerge as in vivo from the excitatory-inhibitory interplay\nand that, unexpectedly, the light stimuli transiently facilitate excitatory\nsynaptic transmission. Of relevance for in vitro models of (dys)functional\ncortical microcircuitry and in vivo manipulations of cell assemblies, we give\nfor the first time evidence of network-level consequences of the alteration of\nsynaptic physiology by optogenetics\n