“School of Biological Sciences”
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| Paper IPM / Biological Sciences / 18106 |
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Several neurological disorders like Parkinsonâ??s disease, essential tremor, and epilepsy are linked to abnormal brain synchrony and/or pathological connectivity. It has been shown that invasive and non-invasive electrical stimulation techniques, e.g., deep brain stimulation (DBS) and transcranial current stimulation (tCS), perturb pathological neural activities and, hypothetically, restore normal information processing. In this Talk, we focus on the role of synaptic plasticity in shaping such normalization during and after delivering electrical pulses. In prior work we have have characterized how DBS modulates dynamics of short-term synaptic plasticity inmice and humans, .and have developed models for replicating long-lasting effects of electrical stimulations. Here we focus on the as-yet unanswered question of how electrical pulses modulate synaptic plasticity at different time scales, and how this understanding can inform the design of novel therapeutic stimulation protocols. Recent pre-clinical and clinical findings suggest that complex spatio-temporal stimulation patterns may promote short-term as well as long-term plasticity in stimulated brain regions. In this work we combined models of short-term and long-term plasticity in a network model of the basal ganglia circuitry, with the aim of identifying neuroplasticity mechanisms at multiple time scales that could be targeted for optimized brain stimulation therapies. We found that the proposed integrated synaptic model can successfully capture the impact of stimulation-induced spike-timing and firing rate changes. Our findings provide testable hypotheses for the improvement of clinically used stimulation techniques, and suggest that both short-and long-term plasticity induced by electrical stimulation are crucial to modulate neuroplasticity, and thus shape functional connectivity across brain regions.
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