Deep brain stimulation of A13 region evokes robust locomotory response in rats.

Abstract

Deep brain stimulation (DBS) is a common therapy for Parkinson's disease (PD) motor symptoms, but gait dysfunction remains a challenge. This study investigated the A13 region of the medial zona incerta (mZI), as a novel target for alleviating gait deficits. We hypothesized that A13-DBS would enhance locomotor activity and promote exploratory behavior in rats. Nine Long-Evans rats were implanted with wireless DBS devices targeting the A13 region. Open-field tests evaluated locomotor responses, with DBS parameters (amplitude, pulse width, and frequency) optimized for locomotion without adverse effects. Locomotor activity was quantified by total distance traveled. Exploratory metrics, including time in the center of the open field and supported rearing counts, were also analyzed. Cellular activation within the A13 region was assessed using c-Fos immunohistochemistry. Computer simulations modeled electric field distribution to estimate the stimulation volume. A13-DBS significantly increased locomotor activity during stimulation, with a sustained elevation poststimulation. Supported rearing, indicative of exploratory behavior, was also significantly increased. Histological analysis confirmed robust activation of A13 region neurons with minimal spread. Simulations estimated electric field spread within 0.7 mm of the electrode tip, indicating targeted stimulation. These findings demonstrate that tuned A13-DBS evokes a robust locomotor response without apparent anxiogenic effects. This suggests the A13 region may be a promising target for managing PD gait dysfunction. Wireless DBS in freely moving rats allowed assessment of open-field behaviors, supporting A13-DBS viability in future studies.NEW & NOTEWORTHY This study demonstrates that deep brain stimulation (DBS) of the A13 region in rats robustly increases locomotor activity without inducing anxiety using a novel wireless stimulation approach. This suggests A13 may be a promising therapeutic target for gait dysfunction in Parkinson's disease. The use of wireless DBS in freely moving rats also provided valuable insights into open field behaviors.