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Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation
Sleep loss disrupts consolidation of hippocampus-dependent memory. To characterize effects of learning and sleep loss, we quantified activity-dependent phosphorylation of ribosomal protein S6 (pS6) across the dorsal hippocampus of mice. We find that pS6 is enhanced in dentate gyrus (DG) following si...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364159/ https://www.ncbi.nlm.nih.gov/pubmed/34344824 http://dx.doi.org/10.1073/pnas.2019318118 |
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author | Delorme, James Wang, Lijing Kuhn, Femke Roig Kodoth, Varna Ma, Jingqun Martinez, Jessy D. Raven, Frank Toth, Brandon A. Balendran, Vinodh Vega Medina, Alexis Jiang, Sha Aton, Sara J. |
author_facet | Delorme, James Wang, Lijing Kuhn, Femke Roig Kodoth, Varna Ma, Jingqun Martinez, Jessy D. Raven, Frank Toth, Brandon A. Balendran, Vinodh Vega Medina, Alexis Jiang, Sha Aton, Sara J. |
author_sort | Delorme, James |
collection | PubMed |
description | Sleep loss disrupts consolidation of hippocampus-dependent memory. To characterize effects of learning and sleep loss, we quantified activity-dependent phosphorylation of ribosomal protein S6 (pS6) across the dorsal hippocampus of mice. We find that pS6 is enhanced in dentate gyrus (DG) following single-trial contextual fear conditioning (CFC) but is reduced throughout the hippocampus after brief sleep deprivation (SD; which disrupts contextual fear memory [CFM] consolidation). To characterize neuronal populations affected by SD, we used translating ribosome affinity purification sequencing to identify cell type–specific transcripts on pS6 ribosomes (pS6-TRAP). Cell type–specific enrichment analysis revealed that SD selectively activated hippocampal somatostatin-expressing (Sst+) interneurons and cholinergic and orexinergic hippocampal inputs. To understand the functional consequences of SD-elevated Sst+ interneuron activity, we used pharmacogenetics to activate or inhibit hippocampal Sst+ interneurons or cholinergic input from the medial septum. The activation of either cell population was sufficient to disrupt sleep-dependent CFM consolidation by gating activity in granule cells. The inhibition of either cell population during sleep promoted CFM consolidation and increased S6 phosphorylation among DG granule cells, suggesting their disinhibition by these manipulations. The inhibition of either population across post-CFC SD was insufficient to fully rescue CFM deficits, suggesting that additional features of sleeping brain activity are required for consolidation. Together, our data suggest that state-dependent gating of DG activity may be mediated by cholinergic input and local Sst+ interneurons. This mechanism could act as a sleep loss–driven inhibitory gate on hippocampal information processing. |
format | Online Article Text |
id | pubmed-8364159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-83641592021-08-24 Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation Delorme, James Wang, Lijing Kuhn, Femke Roig Kodoth, Varna Ma, Jingqun Martinez, Jessy D. Raven, Frank Toth, Brandon A. Balendran, Vinodh Vega Medina, Alexis Jiang, Sha Aton, Sara J. Proc Natl Acad Sci U S A Biological Sciences Sleep loss disrupts consolidation of hippocampus-dependent memory. To characterize effects of learning and sleep loss, we quantified activity-dependent phosphorylation of ribosomal protein S6 (pS6) across the dorsal hippocampus of mice. We find that pS6 is enhanced in dentate gyrus (DG) following single-trial contextual fear conditioning (CFC) but is reduced throughout the hippocampus after brief sleep deprivation (SD; which disrupts contextual fear memory [CFM] consolidation). To characterize neuronal populations affected by SD, we used translating ribosome affinity purification sequencing to identify cell type–specific transcripts on pS6 ribosomes (pS6-TRAP). Cell type–specific enrichment analysis revealed that SD selectively activated hippocampal somatostatin-expressing (Sst+) interneurons and cholinergic and orexinergic hippocampal inputs. To understand the functional consequences of SD-elevated Sst+ interneuron activity, we used pharmacogenetics to activate or inhibit hippocampal Sst+ interneurons or cholinergic input from the medial septum. The activation of either cell population was sufficient to disrupt sleep-dependent CFM consolidation by gating activity in granule cells. The inhibition of either cell population during sleep promoted CFM consolidation and increased S6 phosphorylation among DG granule cells, suggesting their disinhibition by these manipulations. The inhibition of either population across post-CFC SD was insufficient to fully rescue CFM deficits, suggesting that additional features of sleeping brain activity are required for consolidation. Together, our data suggest that state-dependent gating of DG activity may be mediated by cholinergic input and local Sst+ interneurons. This mechanism could act as a sleep loss–driven inhibitory gate on hippocampal information processing. National Academy of Sciences 2021-08-10 2021-08-03 /pmc/articles/PMC8364159/ /pubmed/34344824 http://dx.doi.org/10.1073/pnas.2019318118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Delorme, James Wang, Lijing Kuhn, Femke Roig Kodoth, Varna Ma, Jingqun Martinez, Jessy D. Raven, Frank Toth, Brandon A. Balendran, Vinodh Vega Medina, Alexis Jiang, Sha Aton, Sara J. Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation |
title | Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation |
title_full | Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation |
title_fullStr | Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation |
title_full_unstemmed | Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation |
title_short | Sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation |
title_sort | sleep loss drives acetylcholine- and somatostatin interneuron–mediated gating of hippocampal activity to inhibit memory consolidation |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364159/ https://www.ncbi.nlm.nih.gov/pubmed/34344824 http://dx.doi.org/10.1073/pnas.2019318118 |
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