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Inactivation of the Medial Entorhinal Cortex Selectively Disrupts Learning of Interval Timing.

ABSTRACT: The entorhinal-hippocampal circuit can encode features of elapsed time, but nearly all previous research focused on neural encoding of "implicit time." Recent research has revealed encoding of "explicit time" in the medial entorhinal cortex (MEC) as mice are actively engaged in an interval timing task. However, it is unclear whether the MEC is required for temporal perception and/or learning during such explicit timing tasks. We therefore optogenetically inactivated the MEC as mice learned an interval timing "door stop" task that engaged mice in immobile interval timing behavior and locomotion-dependent navigation behavior. We find that the MEC is critically involved in learning of interval timing but not necessary for estimating temporal duration after learning. Together with our previous research, these results suggest that activity of a subcircuit in the MEC that encodes elapsed time during immobility is necessary for learning interval timing behaviors.

SUBMITTER: Heys JG

PROVIDER: S-EPMC8719477 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Inactivation of the Medial Entorhinal Cortex Selectively Disrupts Learning of Interval Timing.

Heys James G JG Wu Zihan Z Allegra Mascaro Anna Letizia AL Dombeck Daniel A DA

Cell reports 20200901 12

The entorhinal-hippocampal circuit can encode features of elapsed time, but nearly all previous research focused on neural encoding of "implicit time." Recent research has revealed encoding of "explicit time" in the medial entorhinal cortex (MEC) as mice are actively engaged in an interval timing task. However, it is unclear whether the MEC is required for temporal perception and/or learning during such explicit timing tasks. We therefore optogenetically inactivated the MEC as mice learned an in ...[more]

PMID: 32966784

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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

Inactivation of the Medial Entorhinal Cortex Selectively Disrupts Learning of Interval Timing.

Publications

Inactivation of the Medial Entorhinal Cortex Selectively Disrupts Learning of Interval Timing.

Similar Datasets

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