Playing the piano with the cortex: role of neuronal ensembles and pattern completion in perception and behavior

•Holographic optogenetics enable imaging and manipulation of neuronal ensembles.•Neuronal ensembles can be imprinted with Hebbian paradigms.•Activation of pattern completion neurons triggers ensembles.•Recalling of neuronal ensembles can control visually guided behavior. Neuronal ensembles, i.e. coactive groups of neurons, have been long postulated to be functional building blocks of cortical circuits and units of the neural code. Calcium imaging of neuronal populations has demonstrated the widespread existence of spontaneous and sensory-evoked ensembles in cortical circuits in vivo. The development of two-photon optical techniques to simultaneously record and activate neurons with single cell resolution (“piano” experiments) has revealed the existence of pattern completion neurons, which can trigger an entire ensemble, and demonstrated a causal relation between ensembles and behavior. We review recent results controlling visual perception with targeted holographic manipulation of cortical ensembles by stimulating pattern completion neurons. Analyzing population activity as neuronal ensembles and exploiting pattern completion could enable control of brain states in health and disease.