Neuronal ensembles are groups of neurons with coordinated activity that could represent sensory, motor, or cognitive states. The study of how neuronal ensembles are built, recalled, and involved in the guiding of complex behaviors has been limited by the lack of experimental and analytical tools to reliably identify and manipulate neurons that have the ability to activate entire ensembles. Such “pattern completion” neurons have also been proposed as key elements of artificial and biological neural networks. Indeed, the relevance of pattern completion is highlighted by growing evidence that targeting them can activate neuronal ensembles and trigger behavior. As a method to reliably detect pattern completion neurons, we use Conditional Random Fields (CRFs), a type of probabilistic graphical models. We apply CRFs to identify pattern completion neurons in ensembles in experiments using in vivo two-photon calcium imaging from primary visual cortex of male mice and confirm the CRFs predictions with two-photon op...