VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse

IntroductionRecognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the...

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Main Authors: Seung H. Jung, Laura K. Olsen, Krysten A. Jones, Raquel J. Moore, Sean W. Harshman, Candice N. Hatcher-Solis
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Molecular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2024.1452327/full
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author Seung H. Jung
Seung H. Jung
Laura K. Olsen
Laura K. Olsen
Krysten A. Jones
Krysten A. Jones
Raquel J. Moore
Raquel J. Moore
Sean W. Harshman
Candice N. Hatcher-Solis
author_facet Seung H. Jung
Seung H. Jung
Laura K. Olsen
Laura K. Olsen
Krysten A. Jones
Krysten A. Jones
Raquel J. Moore
Raquel J. Moore
Sean W. Harshman
Candice N. Hatcher-Solis
author_sort Seung H. Jung
collection DOAJ
description IntroductionRecognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the effectiveness of multiple sessions of VNS to enhance recognition memory in healthy rodents and the underlying cognitive benefits of VNS by proteomic analysis of the synaptosome.MethodsRats demonstrated VNS-induced recognition memory improvements using a novel object recognition (NOR) task. Using the LC–MS/MS method, roughly 3,000 proteins in the synaptosome of the hippocampus were analyzed.ResultsProtein–protein interaction (PPI) enrichment analysis found differentially expressed proteins related to synaptic signaling and neurotransmitter pathways. PPI network analysis identified six unique protein clusters, including a cluster of synaptic signaling related pathways. Using ingenuity pathway analysis (IPA), rapamycin-insensitive companion of mTOR was identified as an upstream regulator of synaptosome changes due to VNS-paired training.DiscussionBased on these results, it is proposed that VNS may mediate cognitive enhancement via increases in glutamatergic signaling and early LTP during the consolidation period, followed by sustained synaptic plasticity via modified post-synaptic receptor expression and dendritic outgrowth. Further investigation is required to determine if VNS is a good candidate to ameliorate cognitive impairment.
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spelling doaj-art-434cd49f8e2747d694aeb4b26f953db32025-08-20T02:36:18ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-12-011710.3389/fnmol.2024.14523271452327VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapseSeung H. Jung0Seung H. Jung1Laura K. Olsen2Laura K. Olsen3Krysten A. Jones4Krysten A. Jones5Raquel J. Moore6Raquel J. Moore7Sean W. Harshman8Candice N. Hatcher-Solis9Cognitive Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson AFB, OH, United StatesDCS Infoscitex, Dayton, OH, United StatesCognitive Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson AFB, OH, United StatesOak Ridge Institute for Science and Education, Oak Ridge, TN, United StatesCognitive Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson AFB, OH, United StatesIntegrative Health & Performance Sciences, UES, Inc., Blue Halo, Dayton, OH, United StatesCognitive Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson AFB, OH, United StatesDCS Infoscitex, Dayton, OH, United StatesAnalytical Chemistry, 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson AFB, OH, United StatesCognitive Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson AFB, OH, United StatesIntroductionRecognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the effectiveness of multiple sessions of VNS to enhance recognition memory in healthy rodents and the underlying cognitive benefits of VNS by proteomic analysis of the synaptosome.MethodsRats demonstrated VNS-induced recognition memory improvements using a novel object recognition (NOR) task. Using the LC–MS/MS method, roughly 3,000 proteins in the synaptosome of the hippocampus were analyzed.ResultsProtein–protein interaction (PPI) enrichment analysis found differentially expressed proteins related to synaptic signaling and neurotransmitter pathways. PPI network analysis identified six unique protein clusters, including a cluster of synaptic signaling related pathways. Using ingenuity pathway analysis (IPA), rapamycin-insensitive companion of mTOR was identified as an upstream regulator of synaptosome changes due to VNS-paired training.DiscussionBased on these results, it is proposed that VNS may mediate cognitive enhancement via increases in glutamatergic signaling and early LTP during the consolidation period, followed by sustained synaptic plasticity via modified post-synaptic receptor expression and dendritic outgrowth. Further investigation is required to determine if VNS is a good candidate to ameliorate cognitive impairment.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1452327/fullvagus nerve stimulationnovel object recognitionrecognition memoryproteomicssynaptic signalingsynaptic plasticity
spellingShingle Seung H. Jung
Seung H. Jung
Laura K. Olsen
Laura K. Olsen
Krysten A. Jones
Krysten A. Jones
Raquel J. Moore
Raquel J. Moore
Sean W. Harshman
Candice N. Hatcher-Solis
VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse
Frontiers in Molecular Neuroscience
vagus nerve stimulation
novel object recognition
recognition memory
proteomics
synaptic signaling
synaptic plasticity
title VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse
title_full VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse
title_fullStr VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse
title_full_unstemmed VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse
title_short VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse
title_sort vns paired with training enhances recognition memory mechanistic insights from proteomic analysis of the hippocampal synapse
topic vagus nerve stimulation
novel object recognition
recognition memory
proteomics
synaptic signaling
synaptic plasticity
url https://www.frontiersin.org/articles/10.3389/fnmol.2024.1452327/full
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