Brambilla Pisoni, Cecilia, 1993-Muñoz-Moreno, EmmaGallego-Amaro, IanireMaldonado, Rafael, 1961-Ivorra Cano, Antoni, 1974-Soria Rodríguez, GuadalupeOzaita Mintegui, Andrés, 1969-2022-06-212022-06-212022Brambilla-Pisoni C, Muñoz-Moreno E, Gallego-Amaro I, Maldonado R, Ivorra A, Soria G, Ozaita A. Auricular transcutaneous vagus nerve stimulation acutely modulates brain connectivity in mice. Front Cell Neurosci. 2022 Apr 25;16:856855. DOI: 10.3389/fncel.2022.8568551662-5102http://hdl.handle.net/10230/53544Brain electrical stimulation techniques take advantage of the intrinsic plasticity of the nervous system, opening a wide range of therapeutic applications. Vagus nerve stimulation (VNS) is an approved adjuvant for drug-resistant epilepsy and depression. Its non-invasive form, auricular transcutaneous VNS (atVNS), is under investigation for applications, including cognitive improvement. We aimed to study the effects of atVNS on brain connectivity, under conditions that improved memory persistence in CD-1 male mice. Acute atVNS in the cymba conchae of the left ear was performed using a standard stimulation protocol under light isoflurane anesthesia, immediately or 3 h after the training/familiarization phase of the novel object-recognition memory test (NORT). Another cohort of mice was used for bilateral c-Fos analysis after atVNS administration. Spearman correlation of c-Fos density between each pair of the thirty brain regions analyzed allowed obtaining the network of significant functional connections in stimulated and non-stimulated control brains. NORT performance was enhanced when atVNS was delivered just after, but not 3 h after, the familiarization phase of the task. No alterations in c-Fos density were associated with electrostimulation, but a significant effect of atVNS was observed on c-Fos-based functional connectivity. atVNS induced a clear reorganization of the network, increasing the inter-hemisphere connections and the connectivity of locus coeruleus. Our results provide new insights into the effects of atVNS on memory performance and brain connectivity extending our knowledge of the biological mechanisms of bioelectronics in medicine.application/pdfeng© 2022 Brambilla-Pisoni, Muñoz-Moreno, Gallego-Amaro, Maldonado, Ivorra, Soria and Ozaita. 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) and the copyright owner(s) 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fncel.2022.856855Auricular transcutaneous vagus nerve stimulationBrain connectivityc-Fos functional networksElectrostimulationMemory persistenceinfo:eu-repo/semantics/openAccess