{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:00:08Z","timestamp":1782280808612,"version":"3.54.5"},"posted":{"date-parts":[[2025,3,5]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Sleep is critically involved in strengthening memories. However, our understanding of the morphological changes underlying this process is still emerging. Recent studies suggest that specific subsets of dendritic spines are strengthened during sleep in specific neurons involved in recent learning. Contextual memories associated with traumatic experiences are involved in post-traumatic stress disorder (PTSD) and represent recent learning that may be strengthened during sleep. We tested the hypothesis that dendritic spines encoding contextual fear memories are selectively strengthened during sleep. Furthermore, we tested how sleep deprivation after initial fear learning impacts dendritic spines following re-exposure to fear conditioning. We used ArcCreER\n                  <jats:sup>T2<\/jats:sup>\n                  mice to visualize neurons that encode contextual fear learning (Arc+ neurons), and concomitantly labeled neurons that did not encode contextual fear learning (Arc-neurons). Dendritic branches of Arc+ and Arc-neurons were sampled using confocal imaging to assess spine densities using three-dimensional image analysis from either sleep deprived (SD) or control mice allowed to sleep normally. Mushroom spines in Arc+ branches displayed decreased density in SD mice, indicating upscaling of mushroom spines during sleep following fear learning. In comparison, no changes were observed in dendritic spines from Arc-branches. When animals were re-exposed to contextual fear conditioning 4 weeks later, we observed lower density of mushroom spines in both Arc+ and Arc-branches, as well as lower density of thin spines in Arc-branches in mice that were SD following the initial fear conditioning trial. Our findings indicate that sleep strengthens dendritic spines in neurons that recently encoded fear memory, and sleep deprivation following initial fear learning impairs dendritic spine strengthening initially and following later re-exposure. SD following a traumatic experience thus may be a viable strategy in weakening the strength of contextual memories associated with trauma and PTSD.\n                <\/jats:p>","DOI":"10.1101\/2025.03.02.641043","type":"posted-content","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T05:36:19Z","timestamp":1741152979000},"source":"Crossref","is-referenced-by-count":0,"title":["Sleep Deprivation Alters Hippocampal Dendritic Spines in a Contextual Fear Memory Engram"],"prefix":"10.64898","author":[{"given":"Matthew","family":"Tennin","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter T.","family":"Matkins","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Rexrode","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna","family":"Bollavarapu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel D.","family":"Asplund","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Pareek","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kroeger","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Pantazopoulos","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"},{"name":"Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Gisabella","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA"},{"name":"Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041112094509000_2025.03.02.641043v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04286"},{"key":"2026041112094509000_2025.03.02.641043v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.12.025"},{"key":"2026041112094509000_2025.03.02.641043v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2005.05.002"},{"key":"2026041112094509000_2025.03.02.641043v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2934"},{"key":"2026041112094509000_2025.03.02.641043v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5982"},{"key":"2026041112094509000_2025.03.02.641043v1.6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1177\/1073858404270900","article-title":"A molecular window on sleep: changes in gene expression between sleep and wakefulness","volume":"11","year":"2005","journal-title":"The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry"},{"key":"2026041112094509000_2025.03.02.641043v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature08488"},{"key":"2026041112094509000_2025.03.02.641043v1.8","doi-asserted-by":"crossref","unstructured":"Havekes, R. , et al. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1. eLife 5(2016).","DOI":"10.7554\/eLife.13424"},{"key":"2026041112094509000_2025.03.02.641043v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1249098"},{"key":"2026041112094509000_2025.03.02.641043v1.10","doi-asserted-by":"crossref","unstructured":"Renouard, L. , et al. REM sleep promotes bidirectional plasticity in developing visual cortex in vivo. Neurobiol Sleep Circadian Rhythms 12, 100076 (2022).","DOI":"10.1016\/j.nbscr.2022.100076"},{"key":"2026041112094509000_2025.03.02.641043v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18592-5"},{"key":"2026041112094509000_2025.03.02.641043v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4479"},{"key":"2026041112094509000_2025.03.02.641043v1.13","doi-asserted-by":"crossref","unstructured":"Adler, A. , et al. Sleep promotes the formation of dendritic filopodia and spines near learning-inactive existing spines. Proc Natl Acad Sci U S A 118(2021).","DOI":"10.1073\/pnas.2114856118"},{"key":"2026041112094509000_2025.03.02.641043v1.14","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00032.2012"},{"key":"2026041112094509000_2025.03.02.641043v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.09.004"},{"key":"2026041112094509000_2025.03.02.641043v1.16","doi-asserted-by":"crossref","unstructured":"Perusini, J.N. , et al. Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer\u2019s disease mice. Hippocampus (2017).","DOI":"10.1002\/hipo.22756"},{"key":"2026041112094509000_2025.03.02.641043v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22556"},{"key":"2026041112094509000_2025.03.02.641043v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nature13897"},{"key":"2026041112094509000_2025.03.02.641043v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.018"},{"key":"2026041112094509000_2025.03.02.641043v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.10.039"},{"key":"2026041112094509000_2025.03.02.641043v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.08.015"},{"key":"2026041112094509000_2025.03.02.641043v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.94"},{"key":"2026041112094509000_2025.03.02.641043v1.23","doi-asserted-by":"publisher","DOI":"10.1002\/jts.21848"},{"key":"2026041112094509000_2025.03.02.641043v1.24","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.156.6.902"},{"key":"2026041112094509000_2025.03.02.641043v1.25","doi-asserted-by":"publisher","DOI":"10.1037\/0022-006X.68.5.748"},{"key":"2026041112094509000_2025.03.02.641043v1.26","doi-asserted-by":"publisher","DOI":"10.1177\/0886260507301226"},{"key":"2026041112094509000_2025.03.02.641043v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2008.06.006"},{"key":"2026041112094509000_2025.03.02.641043v1.28","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22756"},{"key":"2026041112094509000_2025.03.02.641043v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80591-7"},{"key":"2026041112094509000_2025.03.02.641043v1.30","first-page":"184083","article-title":"New Insights on Retrieval-Induced and Ongoing Memory Consolidation: Lessons from Arc","volume":"2015","year":"2015","journal-title":"Neural plasticity"},{"key":"2026041112094509000_2025.03.02.641043v1.31","doi-asserted-by":"crossref","unstructured":"Rexrode, L. , et al. Regulation of dendritic spines in the amygdala following sleep deprivation. Front Sleep 2(2023).","DOI":"10.3389\/frsle.2023.1145203"},{"key":"2026041112094509000_2025.03.02.641043v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2014.09.002"},{"key":"2026041112094509000_2025.03.02.641043v1.33","first-page":"269","article-title":"Tamoxifen administration to mice","volume":"2015","year":"2015","journal-title":"Cold Spring Harb Protoc"},{"key":"2026041112094509000_2025.03.02.641043v1.34","first-page":"227","article-title":"The estrogen receptor fusion system in mouse models: a reversible switch","volume":"2015","year":"2015","journal-title":"Cold Spring Harb Protoc"},{"key":"2026041112094509000_2025.03.02.641043v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.203"},{"key":"2026041112094509000_2025.03.02.641043v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.136"},{"key":"2026041112094509000_2025.03.02.641043v1.37","doi-asserted-by":"crossref","unstructured":"Burgdorf, J.S. , et al. NMDAR activation regulates the daily rhythms of sleep and mood. Sleep 42(2019).","DOI":"10.1093\/sleep\/zsz135"},{"key":"2026041112094509000_2025.03.02.641043v1.38","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00532.2019"},{"key":"2026041112094509000_2025.03.02.641043v1.39","doi-asserted-by":"crossref","unstructured":"Yuan, R.K. , et al. Differential effect of sleep deprivation on place cell representations, sleep architecture, and memory in young and old mice. Cell Rep 35, 109234 (2021).","DOI":"10.1016\/j.celrep.2021.109234"},{"key":"2026041112094509000_2025.03.02.641043v1.40","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24764"},{"key":"2026041112094509000_2025.03.02.641043v1.41","doi-asserted-by":"crossref","unstructured":"Havekes, R. , et al. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1. Elife 5(2016).","DOI":"10.7554\/eLife.13424"},{"key":"2026041112094509000_2025.03.02.641043v1.42","doi-asserted-by":"publisher","DOI":"10.1002\/cpns.16"},{"key":"2026041112094509000_2025.03.02.641043v1.43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001997"},{"key":"2026041112094509000_2025.03.02.641043v1.44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321869111"},{"key":"2026041112094509000_2025.03.02.641043v1.45","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22829"},{"key":"2026041112094509000_2025.03.02.641043v1.46","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.01.1.1.010.2007"},{"key":"2026041112094509000_2025.03.02.641043v1.47","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3503-07.2007"},{"key":"2026041112094509000_2025.03.02.641043v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-38412-7"},{"key":"2026041112094509000_2025.03.02.641043v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.03.015"},{"key":"2026041112094509000_2025.03.02.641043v1.50","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.09-08-02982.1989"},{"key":"2026041112094509000_2025.03.02.641043v1.51","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0380-19.2019"},{"key":"2026041112094509000_2025.03.02.641043v1.52","doi-asserted-by":"crossref","unstructured":"Wang, L. , et al. Sleep-dependent engram reactivation during hippocampal memory consolidation associated with subregion-specific biosynthetic changes. iScience 27, 109408 (2024).","DOI":"10.1016\/j.isci.2024.109408"},{"key":"2026041112094509000_2025.03.02.641043v1.53","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.627117"},{"key":"2026041112094509000_2025.03.02.641043v1.54","doi-asserted-by":"crossref","unstructured":"Puighermanal, E. , et al. Ribosomal Protein S6 Phosphorylation Is Involved in Novelty-Induced Locomotion, Synaptic Plasticity and mRNA Translation. Frontiers in molecular neuroscience 10, 419 (2017).","DOI":"10.3389\/fnmol.2017.00419"},{"key":"2026041112094509000_2025.03.02.641043v1.55","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000042703.39845.B4"},{"key":"2026041112094509000_2025.03.02.641043v1.56","doi-asserted-by":"crossref","unstructured":"Medina, J.H. & Viola, H . ERK1\/2: A Key Cellular Component for the Formation, Retrieval, Reconsolidation and Persistence of Memory. Frontiers in molecular neuroscience 11, 361 (2018).","DOI":"10.3389\/fnmol.2018.00361"},{"key":"2026041112094509000_2025.03.02.641043v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.12.038"},{"key":"2026041112094509000_2025.03.02.641043v1.58","unstructured":"Spruston, N. & McBain, C.J. Structural and Functional Properties of Hippocampal Neurons. in The Hippocampus Book (eds. Andersen, P. , Morris, R. , Amaral, D.G. , Bliss, T.V. & O\u2019 Keefe, J. ) 133\u2013201 (Oxford Scholarship Online, 2006)."},{"key":"2026041112094509000_2025.03.02.641043v1.59","doi-asserted-by":"publisher","DOI":"10.1101\/lm.033969.113"},{"key":"2026041112094509000_2025.03.02.641043v1.60","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1418309"},{"key":"2026041112094509000_2025.03.02.641043v1.61","doi-asserted-by":"publisher","DOI":"10.1126\/science.aas9204"},{"key":"2026041112094509000_2025.03.02.641043v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.07.003"},{"key":"2026041112094509000_2025.03.02.641043v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2007.04.009"},{"key":"2026041112094509000_2025.03.02.641043v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(03)00162-0"},{"key":"2026041112094509000_2025.03.02.641043v1.65","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5409.1923"},{"key":"2026041112094509000_2025.03.02.641043v1.66","doi-asserted-by":"publisher","DOI":"10.1038\/19978"},{"key":"2026041112094509000_2025.03.02.641043v1.67","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20391"},{"key":"2026041112094509000_2025.03.02.641043v1.68","doi-asserted-by":"publisher","DOI":"10.1101\/lm.48803"},{"key":"2026041112094509000_2025.03.02.641043v1.69","first-page":"401","article-title":"Acute sleep disruption reduces fear memories in male and female mice","volume":"50","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"2026041112094509000_2025.03.02.641043v1.70","doi-asserted-by":"crossref","unstructured":"Pantazopoulos, H. , et al. Circadian Rhythms of Perineuronal Net Composition. eNeuro 7(2020).","DOI":"10.1101\/2020.04.21.053751"},{"key":"2026041112094509000_2025.03.02.641043v1.71","doi-asserted-by":"crossref","unstructured":"Lommen, M.J.J. , Hoekstra, S. , van den Brink, R.H.S. & Lenaert, B. Fear generalization predicts post-traumatic stress symptoms: A two-year follow-up study in Dutch fire fighters. Journal of anxiety disorders 103, 102855 (2024).","DOI":"10.1016\/j.janxdis.2024.102855"},{"key":"2026041112094509000_2025.03.02.641043v1.72","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2016.15121549"},{"key":"2026041112094509000_2025.03.02.641043v1.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.03.061"},{"key":"2026041112094509000_2025.03.02.641043v1.74","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21003"},{"key":"2026041112094509000_2025.03.02.641043v1.75","doi-asserted-by":"crossref","unstructured":"Delorme, J. , et al. Sleep loss drives acetylcholine- and somatostatin interneuron-mediated gating of hippocampal activity to inhibit memory consolidation. Proc Natl Acad Sci U S A 118(2021).","DOI":"10.1073\/pnas.2019318118"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.02.641043","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:07:58Z","timestamp":1782277678000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.03.02.641043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":75,"URL":"https:\/\/doi.org\/10.1101\/2025.03.02.641043","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41598-026-41336-2","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,3,5]]},"subtype":"preprint"}}