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]. While location is known to be encoded by a plethora of spatially tuned cell types in this brain region[2-6], little is known about how the activity of entorhinal cells is tied together over time. Among the brain's most powerful mechanisms for neural coordination are network oscillations, which dynamically synchronize neural activity across circuit elements[7-10]. In MEC, theta and gamma oscillations provide temporal structure to the neural population activity at subsecond time scales[1,11-13]. 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.

Uncovering 2-D toroidal representations in grid cell ensemble activity during 1-D behavior

“…We look forward to future studies that embrace the toroidal (rather than 2-D spatial) nature of grid cells, which can be studied with a vast array of experimental methods in head-fixed 1-D and virtual environments [59, 60]. These simple task settings come with a number of benefits such as highthroughput experiments with large or movement-sensitive equipment, detailed animal tracking and permit trial-based, stereotyped analyses [11, 14].…”

Modeled grid cells aligned by a flexible attractor

“…In a recent experiment, mice were trained to run head-fixed at a free pace on a rotating wheel, in complete darkness and with no other sensory or behavioral feedback (Gonzalo Cogno et al, 2022). It could be expected that in such a situation the population activity deprived of inputs is influenced to a greater extent by its internal dynamics, offering a window, however imperfect, into the architecture of the attractor.…”

“…Third, the mechanisms behind the formation and maintenance of such a complex and fine-tuned network are far from understood, and theoretical proposals tend to involve as a prerequisite an independent functional representation of two-dimensional space to serve as a tutor (Si & Treves, 2013;Widloski & Fiete, 2014). Fourth, a recent experiment shows that when animals are trained to navigate deprived from sensory and vestibular feedback, entorhinal cells tend to develop a surprising ring (1D) rather than toroidal (2D) population dynamic (Gonzalo Cogno et al, 2022).…”

REM sleep has minute-scale rhythms in mice and humans: A non-binary continuum between phasic and tonic microstates

“…These infraslow-based resting state networks are known to be dynamically modulated in a manner correlated with brain state (Picchioni et al, 2011), and infraslow rhythms in humans during video game performance predict behavioral performance (Monto et al, 2008; Sihn and Kim, 2022). Additionally, markers of NREM sleep in rodents and humans (including thalamic noradrenaline and sleep spindles), as well as oscillatory sequences during WAKE in medial entorhinal cortex (involved in episodic memory formation), are all coordinated at infraslow periodicity (Cogno et al, 2022; Lecci et al, 2017; Osorio-Forero et al, 2021). Thus, infraslow rhythms are becoming an increasing point of focus in cognitive and sleep neuroscience, given its omnipresence across brain states, species and techniques.…”