Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events

Summary: We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampu...

Full description

Bibliographic Details
Main Authors: Maanasa Jayachandran, Stephanie B. Linley, Maximilian Schlecht, Stephen V. Mahler, Robert P. Vertes, Timothy A. Allen
Format: Article
Language:English
Published: Elsevier 2019-07-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719308265
_version_ 1819212470911238144
author Maanasa Jayachandran
Stephanie B. Linley
Maximilian Schlecht
Stephen V. Mahler
Robert P. Vertes
Timothy A. Allen
author_facet Maanasa Jayachandran
Stephanie B. Linley
Maximilian Schlecht
Stephen V. Mahler
Robert P. Vertes
Timothy A. Allen
author_sort Maanasa Jayachandran
collection DOAJ
description Summary: We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here, we used an hM4Di synaptic-silencing approach to test our hypothesis that specific mPFC→RE and mPFC→PER projections regulate sequence memory retrieval. First, we found non-overlapping populations of mPFC cells project to RE and PER. Second, suppressing mPFC activity impaired sequence memory. Third, inhibiting mPFC→RE and mPFC→PER pathways effectively abolished sequence memory. Finally, a sequential lag analysis showed that the mPFC→RE pathway contributes to a working memory retrieval strategy, whereas the mPFC→PER pathway supports a temporal context memory retrieval strategy. These findings demonstrate that mPFC→RE and mPFC→PER pathways serve as top-down mechanisms that control distinct sequence memory retrieval strategies. : Jayachandran et al. demonstrate that the medial prefrontal cortex has separate projections to the nucleus reuniens of the thalamus and perirhinal cortex. The authors then demonstrate that these pathways differentially control how an episodic-like memory is retrieved. Keywords: thalamus, nucleus reuniens, perirhinal cortex, DREADDs, episodic memory, memory retrieval, working memory, temporal context, cognitive control, hippocampus
first_indexed 2024-12-23T06:43:29Z
format Article
id doaj.art-ae1fd666982347328cc5010d28b30873
institution Directory Open Access Journal
issn 2211-1247
language English
last_indexed 2024-12-23T06:43:29Z
publishDate 2019-07-01
publisher Elsevier
record_format Article
series Cell Reports
spelling doaj.art-ae1fd666982347328cc5010d28b308732022-12-21T17:56:38ZengElsevierCell Reports2211-12472019-07-01283640654.e6Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of EventsMaanasa Jayachandran0Stephanie B. Linley1Maximilian Schlecht2Stephen V. Mahler3Robert P. Vertes4Timothy A. Allen5Cognitive Neuroscience Program, Department of Psychology, Florida International University, Miami, FL 33199, USACenter for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, FL 33431, USACognitive Neuroscience Program, Department of Psychology, Florida International University, Miami, FL 33199, USADepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697, USACenter for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, FL 33431, USACognitive Neuroscience Program, Department of Psychology, Florida International University, Miami, FL 33199, USA; Department of Environmental Health Sciences, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, FL 33199, USA; Corresponding authorSummary: We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here, we used an hM4Di synaptic-silencing approach to test our hypothesis that specific mPFC→RE and mPFC→PER projections regulate sequence memory retrieval. First, we found non-overlapping populations of mPFC cells project to RE and PER. Second, suppressing mPFC activity impaired sequence memory. Third, inhibiting mPFC→RE and mPFC→PER pathways effectively abolished sequence memory. Finally, a sequential lag analysis showed that the mPFC→RE pathway contributes to a working memory retrieval strategy, whereas the mPFC→PER pathway supports a temporal context memory retrieval strategy. These findings demonstrate that mPFC→RE and mPFC→PER pathways serve as top-down mechanisms that control distinct sequence memory retrieval strategies. : Jayachandran et al. demonstrate that the medial prefrontal cortex has separate projections to the nucleus reuniens of the thalamus and perirhinal cortex. The authors then demonstrate that these pathways differentially control how an episodic-like memory is retrieved. Keywords: thalamus, nucleus reuniens, perirhinal cortex, DREADDs, episodic memory, memory retrieval, working memory, temporal context, cognitive control, hippocampushttp://www.sciencedirect.com/science/article/pii/S2211124719308265
spellingShingle Maanasa Jayachandran
Stephanie B. Linley
Maximilian Schlecht
Stephen V. Mahler
Robert P. Vertes
Timothy A. Allen
Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events
Cell Reports
title Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events
title_full Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events
title_fullStr Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events
title_full_unstemmed Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events
title_short Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events
title_sort prefrontal pathways provide top down control of memory for sequences of events
url http://www.sciencedirect.com/science/article/pii/S2211124719308265
work_keys_str_mv AT maanasajayachandran prefrontalpathwaysprovidetopdowncontrolofmemoryforsequencesofevents
AT stephanieblinley prefrontalpathwaysprovidetopdowncontrolofmemoryforsequencesofevents
AT maximilianschlecht prefrontalpathwaysprovidetopdowncontrolofmemoryforsequencesofevents
AT stephenvmahler prefrontalpathwaysprovidetopdowncontrolofmemoryforsequencesofevents
AT robertpvertes prefrontalpathwaysprovidetopdowncontrolofmemoryforsequencesofevents
AT timothyaallen prefrontalpathwaysprovidetopdowncontrolofmemoryforsequencesofevents