Using a new and improved optogenetic technique, researchers report the ability to control - and even create - novel visual experiences in the brains of living mice, even in the absence of natural sensory input, according to a new study. The results not only broaden our understanding of how the perceptions of the outside world are initiated and manifested in living mammalian brains but could also aid in the development of neurotherapeutics for those who suffer neuropsychiatric symptoms like hallucinations or delusions. Perceptual experiences of the surrounding environment likely stem from sensory-driven neuronal activity patterns in the mammalian neocortex. However, the relationships between this activity and its influence on perception and behavior remain unclear. While there has been significant scientific interest in the ability to study and perhaps influence perception and behavior through optogenetics, technological limitations have made progress towards these goals difficult, according to the authors. To overcome these challenges, James Marshel and colleagues developed a new optogenetic technique capable of individual-cell observation and control of hundreds of neurons across a mouse neocortex. Through genome mining of more than 600 microbial genomes, Marshel et al. identified a new channelrhodopsin (ChRmine) with exceptional optogenetic properties. Combined with an improved holographic photostimulation technique, this allowed the researchers to deeply probe - and even elicit - activity within the visual cortex of living mice. According to the results, optogenetic stimulation of specific neuron ensembles previously activated by natural perception of visual stimuli recreated the original activity, suggesting the ability to successfully elicit perception and guide behavior in mice. What's more, the new optogenetic method's ability to examine activity spanning large cortex volumes revealed new insights into the dynamics of neuronal activity between cortical layers and the neurobiology that underpins mammalian behavior.