Differential Effects of Short-term and Long-term Deep Brain Stimulation on Striatal Neuronal Excitability in a Dystonia Animal Model

Abstract

Deep brain stimulation (DBS) is, by now, one of the standard treatment options for movement disorders like dystonia or Parkinsons Disease. Although its clinical effectiveness is established, the exact mechanisms by which DBS influences neural motor networks are not fully understood. The present study explores the development of adaptive network mechanisms with DBS in the dtsz hamster model, an in-vivo model exhibiting spontaneous dystonic episodes, by comparing functional impacts of short-term and long-term DBS on medium spiny neurons (MSNs) and synaptic transmission in the striatum. In this electrophysiological study, we uncovered contrasting changes in neuronal excitability and synaptic dynamics following short-term versus long-term DBS. Short-term DBS enhanced neuronal firing responses, while long-term DBS diminished them. Regarding synaptic alterations, both short-term and long-term DBS significantly shifted spontaneous EPSC occurrences to longer intervals, with this effect, however, being more pronounced in short-term DBS, leading to a significant decrease in mEPSC frequency. Notably, acetylcholine application effectively reversed this effect, restoring mEPSC frequency more efficiently again in tissue subjected to short-term DBS compared to long-term DBS. These observations indicate that the therapeutic benefits of DBS in dystonia may involve both immediate and adaptive mechanisms, which has implications for improving stimulation parameters and treatment protocols. The findings shed light on the temporal specificity of DBS effects and highlight the importance of understanding synaptic mechanisms to enhance therapeutic outcomes for dystonia patients.