Temporal Interval Learning in Cortical Cultures Is Encoded in Intrinsic Network Dynamics.

Telling time and anticipating when external events will happen is among the most important tasks the brain performs. Yet the neural mechanisms underlying timing remain elusive. One theory proposes that timing is a general and intrinsic computation of cortical circuits. We tested this hypothesis using electrical and optogenetic stimulation to determine if brain slices could "learn" temporal intervals. Presentation of intervals between 100 and 500 ms altered the temporal profile of evoked network activity in an interval and pathway-specific manner-suggesting that the network learned to anticipate an expected stimulus. Recordings performed during training revealed a progressive increase in evoked network activity, followed by subsequent refinement of temporal dynamics, which was related to a time-window-specific increase in the excitatory-inhibitory balance. These results support the hypothesis that subsecond timing is an intrinsic computation and that timing emerges from network-wide, yet pathway-specific, changes in evoked neural dynamics.