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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Neuroplasticity and Development
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1452327

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

Provisionally accepted
Seung H Jung Seung H Jung 1,2Laura K Olsen Laura K Olsen 1,3*Krysten A Jones Krysten A Jones 1,4*Raquel J Moore Raquel J Moore 1,2Sean W Harshman Sean W Harshman 1Candice N Hatcher-Solis Candice N Hatcher-Solis 1
  • 1 Air Force Research Laboratory, Dayton, United States
  • 2 DCS Corporation (United States), Alexandria, Virginia, United States
  • 3 Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, Tennessee, United States
  • 4 UES, Inc., Dayton, Ohio, United States

The final, formatted version of the article will be published soon.

    Recognition 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. Rats 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. Protein-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. Based 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.

    Keywords: Vagus Nerve Stimulation, Novel object recognition, recognition memory, Proteomics, Synaptic Signaling, synaptic plasticity

    Received: 20 Jun 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Jung, Olsen, Jones, Moore, Harshman and Hatcher-Solis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Laura K Olsen, Air Force Research Laboratory, Dayton, United States
    Krysten A Jones, Air Force Research Laboratory, Dayton, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.