Minute-scale oscillatory sequences in medial entorhinal cortex

The medial entorhinal cortex (MEC) hosts many of the brains circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. While location is known to be encoded by a plethora of spatially tuned cell types in this brain region2-6, little is known about how the activity of entorhinal cells is tied together over time. Among the brains most powerful mechanisms for neural coordination are network oscillations, which dynamically synchronize neural activity across circuit elements7-10. In MEC, theta and gamma oscillations provide temporal structure to the neural population activity at subsecond time scales1,11-13. It remains an open question, however, whether similarly powerful coordination occurs in MEC at behavioural time scales, in the second-to-minute regime. Here we show that MEC activity can be organized into a minute-scale oscillation that entrains nearly the entire cell population, with periods ranging from 10 to 100 seconds. Throughout this ultraslow oscillation, neural activity progresses in periodic and stereotyped sequences. This activity was elicited while mice ran at free pace on a rotating wheel in darkness, with no change in its location or running direction and no scheduled rewards. The oscillation sometimes advanced uninterruptedly for tens of minutes, transcending epochs of locomotion and immobility. Similar oscillatory sequences were not observed in neighboring parasubiculum or in visual cortex. The ultraslow oscillation of activity sequences in MEC may have the potential to couple its neurons and circuits across extended time scales and to serve as a scaffold for processes that unfold at behavioural time scales, such as navigation and episodic memory formation.