Dataset Information

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 experience¹. 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.

SUBMITTER: Gonzalo Cogno S

PROVIDER: S-EPMC10781645 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Minute-scale oscillatory sequences in medial entorhinal cortex.

Gonzalo Cogno Soledad S Obenhaus Horst A HA Lautrup Ane A Jacobsen R Irene RI Clopath Claudia C Andersson Sebastian O SO Donato Flavio F Moser May-Britt MB Moser Edvard I EI

Nature 20231220 7994

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<sup>1</sup>. Whereas location is known to be encoded by spatially tuned cell types in this brain region<sup>2,3</sup>, 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 sh ...[more]

PMID: 38123682

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Project description:The hippocampal region has long been considered critical for memory of time, and recent evidence shows that network operations and single-unit activity in the hippocampus and medial entorhinal cortex (MEC) correlate with elapsed time. However, whether MEC activity is necessary for timing remains largely unknown. Here we expressed DREADDs (designer receptors exclusively activated by designer drugs) under the CaMKIIa promoter to preferentially target MEC excitatory neurons for chemogenetic silencing, while freely moving male rats reproduced a memorized time interval by waiting inside a region of interest. We found that such silencing impaired the reproduction of the memorized interval and led to an overestimation of elapsed time. Trial history analyses under this condition revealed a reduced influence of previous trials on current waiting times, suggesting an impairment in maintaining temporal memories across trials. Moreover, using GLM (logistic regression), we show that decoding behavioral performance from preceding waiting times was significantly compromised when MEC was silenced. In addition to revealing an important role of MEC excitatory neurons for timing behavior, our results raise the possibility that these neurons contribute to such behavior by holding temporal information across trials.SIGNIFICANCE STATEMENT Medial temporal lobe (MTL) structures are implicated in processing temporal information. However, little is known about the role MTL structures, such as the hippocampus and the entorhinal cortex, play in perceiving or reproducing temporal intervals. By chemogenetically silencing medial entorhinal cortex (MEC) excitatory activity during a timing task, we show that this structure is necessary for the accurate reproduction of temporal intervals. Furthermore, trial history analyses suggest that silencing MEC disrupts memory mechanisms during timing. Together, these results suggest that MEC is necessary for timing behavior, possibly by representing the target interval in memory.

Dataset Information

Minute-scale oscillatory sequences in medial entorhinal cortex.

Publications

Minute-scale oscillatory sequences in medial entorhinal cortex.

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