HFS and the brain : multiscale effects of electrical stimulation on a neurotransmitter system Abstract: Electrical deep brain stimulation has long been used as a therapeutic procedure to treat patients suffering from motor symptoms associated with neurological disorders such as Parkinson’s disease. However the mechanism of action by which it operates is poorly understood with several conflicting hypothesis on its rationale. Illuminating this question might help us understand how and why secondary side effects such as depression and suicidality occur in some patients undergoing electrical high frequency stimulation.<br><br>In this study based on previously reported results from our research group the activation of the GABAergic system was studied from a microscopic scale to the effects that it has at a macroscopic behaving scale. We made use of the patch clamp technique to quantify the effects on the microscopic scale. While this quantification is possible using a system with extremely high signal to noise ratio it becomes a larger problem when the mechanism is to be studied in animal models of disease using conventional electrophysiology systems. The exploration of the algorithms used to bypass this problem showed us that the usage of these techniques cannot be blindly made with additional validation techniques to verify that the data recorded is complete. <br><br>To this end other measurement modalities were made use of to study the cascading effects in the brain as a result of the GABA activation to study neurochemical and behavioral changes that occur due to electrical high frequency stimulation. We were able to see that the electrical stimulation did induce reduction in the extracellular levels of neurotransmitter responsible for mood regulation and a corresponding change in the behavior profile was also observed.<br><br>Taken together the results presented in this thesis helps further the idea that a selective activation of the GABAergic system is responsible for the effect that electrical stimulation has on neuronal tissue with specific activation of the axonal elements <br>which are the GABAergic axons. This activation is not limited to a microscopic level but also to a mesoscopic level which then leads to cascading effects that lead to significant behavioral changes all mediated through the GABAergic system