RT Journal Article SR Electronic T1 Noninvasive Brain Stimulation Enhances Memory Acquisition and Is Associated with Synaptoneurosome Modification in the Rat Hippocampus JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0311-19.2019 DO 10.1523/ENEURO.0311-19.2019 VO 6 IS 6 A1 Jung, Seung Ho A1 Hatcher-Solis, Candice A1 Moore, Raquel A1 Bechmann, Naomi A1 Harshman, Sean A1 Martin, Jennifer A1 Jankord, Ryan YR 2019 UL http://www.eneuro.org/content/6/6/ENEURO.0311-19.2019.abstract AB Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation approach previously shown to enhance memory acquisition, but more studies are needed to elucidate the underlying mechanisms. Here, we examined the effects of anodal tDCS (0.25 mA for 30 min) on the memory performance of male Sprague Dawley rats in the passive avoidance test (PAT) and the associated modifications to the hippocampal proteomes. Results indicate anodal tDCS applied before the acquisition period significantly enhanced memory performance in the PAT. Following PAT, synaptoneurosomes were biochemically purified from the hippocampi of tDCS-treated or sham-treated rats and individual protein abundances were determined by bottom-up liquid chromatography mass spectrometry analysis. Proteomic analysis identified 184 differentially expressed hippocampal proteins when comparing the sham to the tDCS before memory acquisition treatment group. Ingenuity pathway analysis (IPA) showed anodal tDCS before memory acquisition significantly enhanced pathways associated with memory, cognition, learning, transmission, neuritogenesis, and long-term potentiation (LTP). IPA identified significant upstream regulators including bdnf, shank3, and gsk3b. Protein-protein interaction (PPI) and protein sequence similarity (PSS) networks show that glutamate receptor pathways, ion channel activity, memory, learning, cognition, and long-term memory were significantly associated with anodal tDCS. Centrality measures from both networks identified key proteins including dlg, shank, grin, and gria that were significantly modified by tDCS applied before the acquisition period. Together, our results provide descriptive molecular evidence that anodal tDCS enhances memory performance in the PAT by modifying hippocampal synaptic plasticity related proteins.