A scalable hippocampal code for flexible interval timing through persistent activity

The brain's ability to accurately estimate time across various intervals is crucial for flexible behavior. Through the discovery of "time cells", the hippocampus has emerged as a critical region for temporal processing. However, the hippocampal dynamics underlying flexible interval timing remain elusive. Here, utilizing behavioral perturbations, two-photon calcium imaging, and extracellular recordings in dorsal CA1, we identified a previously unknown pyramidal neuron subpopulation that flexibly scales its activity during interval timing. As mice performed a time-estimation task, CA1 time cells were scarce during the delay period. In contrast, persistently active cells (PACs) exhibited sustained activity from the onset of timing until the animal's behavioral response. PACs demonstrated temporal scaling: their activity stretched or compressed both with trial-to-trial variations in response time and across different delay durations. PACs comprised two subgroups with complementary ramping dynamics, and their population activity supported reliable decoding of elapsed time. Furthermore, PAC prevalence increased as behavior improved with learning, consistent with their behavioral relevance. Together, these findings revealed scalable sustained dynamics that complement canonical time cell sequences, providing a distinct hippocampal mechanism to support flexible timing behavior.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-04-15
DOI
https://doi.org/10.64898/2026.04.12.716593
Primary Topic
Neuroscience and Music Perception
Type
article
Field-Weighted Citation Impact
0.00

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article

A scalable hippocampal code for flexible interval timing through persistent activity

Raphael Heldman, Zhuoyang Ye, Yingxue Wang, Kori Citrin
bioRxiv (Cold Spring Harbor Laboratory)
Neuroscience and Music Perception
article

A scalable hippocampal code for flexible interval timing through persistent activity

Raphael Heldman, Zhuoyang Ye, Yingxue Wang, Kori Citrin
article en

Abstract

The brain's ability to accurately estimate time across various intervals is crucial for flexible behavior. Through the discovery of "time cells", the hippocampus has emerged as a critical region for temporal processing. However, the hippocampal dynamics underlying flexible interval timing remain elusive. Here, utilizing behavioral perturbations, two-photon calcium imaging, and extracellular recordings in dorsal CA1, we identified a previously unknown pyramidal neuron subpopulation that flexibly scales its activity during interval timing. As mice performed a time-estimation task, CA1 time cells were scarce during the delay period. In contrast, persistently active cells (PACs) exhibited sustained activity from the onset of timing until the animal's behavioral response. PACs demonstrated temporal scaling: their activity stretched or compressed both with trial-to-trial variations in response time and across different delay durations. PACs comprised two subgroups with complementary ramping dynamics, and their population activity supported reliable decoding of elapsed time. Furthermore, PAC prevalence increased as behavior improved with learning, consistent with their behavioral relevance. Together, these findings revealed scalable sustained dynamics that complement canonical time cell sequences, providing a distinct hippocampal mechanism to support flexible timing behavior.

bioRxiv (Cold Spring Harbor Laboratory)
Jupiter Medical Center (US), Max Planck Florida Institute for Neuroscience (US), Florida Atlantic University (US)
National Institute of Mental Health
Openalex Percentile: Top 23%
Neuroscience and Music Perception
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