Re-evaluating Circuit Mechanisms Underlying Pattern Separation

When animals interact with complex environments, their neural circuits must separate overlapping patterns of activity that represent sensory and motor information. Pattern separation is thought to be a key function of several brain regions, including the cerebellar cortex, insect mushroom body, and dentate gyrus. However, recent findings have questioned long-held ideas on how these circuits perform this fundamental computation. Here, we re-evaluate the functional and structural mechanisms underlying pattern separation. We argue that the dimensionality of the space available for population codes representing sensory and motor information provides a common framework for understanding pattern separation. We then discuss how these three circuits use different strategies to separate activity patterns and facilitate associative learning in the presence of trial-to-trial variability. Pattern separation is a fundamental neural computation thought to facilitate associative learning. Cayco-Gajic and Silver review recent theoretical and experimental advances on the key determinants of pattern separation in the cerebellar cortex, insect mushroom body, and dentate gyrus.