Brambilla-Pisoni Cecilia, Muñoz-Moreno Emma, Gallego-Amaro Ianire, Maldonado Rafael, Ivorra Antoni, Soria Guadalupe, Ozaita Andrés
Laboratory of Neuropharmacology, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Experimental 7T MRI Unit, Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
Front Cell Neurosci. 2022 Apr 25;16:856855. doi: 10.3389/fncel.2022.856855. eCollection 2022.
Brain 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 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.
脑电刺激技术利用了神经系统的内在可塑性，开启了广泛的治疗应用。迷走神经刺激（VNS）是一种已获批准用于耐药性癫痫和抑郁症的辅助治疗方法。其非侵入性形式，即耳经皮VNS（atVNS），正在研究用于包括改善认知在内的各种应用。我们旨在研究在改善CD-1雄性小鼠记忆持久性的条件下，atVNS对脑连接性的影响。在轻度异氟烷麻醉下，使用标准刺激方案在左耳进行急性atVNS，在新颖物体识别记忆测试（NORT）的训练/熟悉阶段之后立即或3小时后进行。另一组小鼠在给予atVNS后用于双侧c-Fos分析。分析的30个脑区中每对之间的c-Fos密度的Spearman相关性允许获得受刺激和未受刺激对照脑中显著功能连接的网络。当在任务的熟悉阶段之后立即而非3小时后给予atVNS时，NORT表现得到增强。c-Fos密度的变化与电刺激无关，但观察到atVNS对基于c-Fos的功能连接有显著影响。atVNS诱导了网络的明显重组，增加了半球间连接和蓝斑的连接性。我们的结果为atVNS对记忆表现和脑连接性的影响提供了新的见解，扩展了我们对医学中生物电子学生物学机制的认识。
