Revealing neural correlates of behavior without behavioral measurements

Measuring neuronal tuning curves has been instrumental for many discoveries in neuroscience but requires a-priori assumptions regarding the identity of the encoded variables. We applied unsupervised learning to large-scale neuronal recordings in behaving mice from circuits involved in spatial cognition, and uncovered a highly-organized internal structure of ensemble activity patterns. This emergent structure allowed defining for each neuron an internal tuning-curve that characterizes its activity relative to the network activity, rather than relative to any pre-defined external variable - revealing place-tuning in the hippocampus and head-direction tuning in the thalamus and postsubiculum, without relying on measurements of place or head-direction. Similar investigation in prefrontal cortex revealed schematic representations of distances and actions, and exposed a previously unknown variable, the trajectory-phase. The structure of ensemble activity patterns was conserved across mice, allowing using one animals data to decode another animals behavior. Thus, the internal structure of neuronal activity itself enables reconstructing internal representations and discovering new behavioral variables hidden within a neural code.