Time cell sequences during delay intervals are not dependent on brain state and do not support hippocampus-dependent working memory

Li Yuan, Jose F. Figueroa, Ameen Khan, Gautam Narayan, Jill K. Leutgeb () and Stefan Leutgeb ()
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Li Yuan: University of California San Diego
Jose F. Figueroa: University of California San Diego
Ameen Khan: University of California San Diego
Gautam Narayan: University of California San Diego
Jill K. Leutgeb: University of California San Diego
Stefan Leutgeb: University of California San Diego

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Working memory (WM) is essential for performing cognitive tasks, and sequentially active hippocampal cells over many seconds (‘time cells’) have been observed during WM retention. Time cells predominantly occur when neural activity oscillates at theta frequency. To examine whether time cells during WM maintenance depend on ongoing theta oscillations, we controlled the persistence of theta during 10 s and 30 s delay intervals by either having rats run or rest, which resulted in conditions with and without persistent theta oscillations. In either condition, reliable time cells were limited to only the first few seconds of the delay interval while a second population of constitutively active cells emerged during the remainder of the delay period, neither of which were memory-related. Our results show that hippocampal sequential activity patterns are short-lasting and uninformative for WM, and that WM retention over more than ~5 s needs to include mechanisms other than hippocampal time cells.

Date: 2025
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DOI: 10.1038/s41467-025-62498-z

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