Introduction: While the mechanisms underlying the effects of DBS in dystonia are poorly understood, changes in neural plasticity may play a role. In a pilot study, PSA-NCAM staining was observed in animals subjected to 7 days of GPi-DBS, and was associated with improved motor coordination and more spontaneous locomotor activity (Inan, et al, 2010). Therefore, we resolved to determine the effects and time course of GPi-DBS on motor behavior and whether GPi-DBS affects the expression of factors involved in neural plasticity, including PSA-NCAM, NF200 and GFAP.

Methods: Electrodes were implanted in the entopeduncular nucleus in adult male Sprague-Dawley rats, which were then assigned to 3 groups: 1) 4 hours, 2) 7 days and 3) 28 days (N=6 each). DBS was applied to 4 animals per group; 2 served as unstimulated controls. All rats were subjected to the open field, cylinder and horizontal ladder tests pre-operatively, on post-operative day 4, and weekly. Rats were then sacrificed, their brains harvested and fixed in paraformaldehyde, cryosectioned at 40 mm intervals, stained for PSA-NCAM, NF200 and GFAP expression and examined under fluorescence microscopy.

Results: Total distance travelled within the open field was significantly greater for DBS-stimulated animals over the timepoints assessed (p<0.001). There was also a significant interaction of treatment and time for the percentage of time spent in the middle of the open field (p=0.048). PSA-NCAM expression was not significantly altered by DBS, while immunohistochemistry for GFAP and NF200 is currently ongoing.

Conclusions: These findings suggest that chronic GPi-DBS does not influence motor coordination in healthy rats. However, the observed increase in exploratory activity suggests the possibility of an anxiolytic effect, which has been observed after stimulation of the VL thalamus. Our findings further suggest that chronic GPi-DBS does not induce PSA-NCAM expression, though its effects on plasticity and glial activation are currently pending.

Patient Care: This research will help us to better understand the mechanisms and long-term effects of GPi-DBS in improving dystonia, and thereby provide an understanding of the cellular effects and the basis for future developments in DBS for other brain regions and conditions.

Learning Objectives: By the conclusion of this session, participants should be able to appreciate the evidence underpining a role for plasticity in DBS for dystonia, and understand the experimental processes involved in elucidating this role in vivo.

References: Inan SY, Dyck R, Kiss ZHT. (2010) Chronic high-frequency stimulation in the rat basal ganglia: behaviour and histology. Soc. Neurosci. Abstr. Program No. 755.12