Brainplasticity can be enhanced by modulation of brainstem nuclei through stimulation of the tenth cranial nerve (vagus nerve stimulation, VNS). When VNS is repeatedly paired with a specific sensory input, a more widespread neuronal network is recruited. This project will test the hypothesis that repeated pairing of VNS with electrical activation of specific brain networks increases the number of neurons, and thus the size of the neuronal network, that respond to that electrical stimulation. (WP1). This project will also investigate whether pairing VNS with deep brain stimulation (DBS) of the hippocampus can enhance the subsequent modulatory effect of the hippocampal stimulation on hippocampal network activity in order to evaluate whether VNS is able to increase the therapeutic efficacy of DBS using the plasticity-promoting effects of VNS (WP2). Enhancing the therapeutic efficacy of DBS could have a major impact for the many patients with uncontrolled epileptic seizures (about 20% of patients with epilepsy, i.e. 680,000 patients in Europe). This project will therefor evaluate whether this approach enhances the therapeutic, antiepileptic effects of hippocampal DBS in a rat model for temporal lobe epilepsy (TLE) (WP3).