A functionally relevant and long-term model of deep brain stimulation of the rat subthalamic nucleus: advantages and considerations

In this review we outline some relevant considerations with regards to the rat model of deep brain stimulation of the subthalamic nucleus (STN DBS). In order to optimize the rat STN DBS model in terms of predictive validity for the clinical situation we propose that the STN stimulation experimental design parameters in rodents should incorporate the following features: (i) stimulation parameters that demonstrate functional alleviation of symptoms induced by nigrostriatal dopamine (DA) denervation; (ii) stimulation duration that is relatively long-term and continuous; (iii) stimulation that is initiated at a time when the denervation status of the nigrostriatal system is known to be partial and progressing; (iv) stimulation current spread that is minimized and optimized to closely approximate the clinical situation; (v) the appropriate control conditions are included; and (vi) implantation to the STN target is verified post-mortem. Further research that examines the effect of long-term STN DBS on the neurophysiology and neurochemistry of STN circuitry is warranted. The rat model of functionally relevant long-term STN DBS provides a most favorable preclinical experimental platform in which to conduct these studies.