Minute-scale oscillatory sequences in medial entorhinal cortex

Abstract The medial entorhinal cortex (MEC) hosts many of the brain’s circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience 1 . Whereas location is known to be encoded by spatially tuned cell types in this brain region 2,3 , little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.