Electrical and chemical modulation of Adult Hippocampal Neurogenesis

Abstract

Background: Despite the advances in technology that has steered clinical trials to new approaches and surgical modalities, the basic scientific knowledge of how these technologies work is still controversial. Deep brain stimulation (DBS), for example, has developed during the past 20 years, providing substantial clinical benefit for a variety of movement disorders such as Parkinson’s disease, essential tremor and dystonia. It is, however, still unknown how DBS alters neural activity and the neuronal electrophysiology to induce beneficial outcomes. One area of interest is to investigate a possible role for modulation of adult hippocampal neurogenesis in mediating DBS effects. The hippocampus is a structural and functional component of the limbic system and is known to be a neurogenic niche containing neural stem-progenitor cells in the subgranular zone (SGZ) of the dentate gyrus (DG). It possesses extensive interconnections with the anteromedial thalamic nucleus (AMN) proposing that electrical stimulation of the AMN conveys physiological fluctuations to the hippocampus and possibly elicits neurogenesis. The specificity of the electrical signal is dubious, however, and it results in inadvertent stimulation to nearby regions and to the passing fibers. Therefore, a more specific targeting of the AMN cell bodies might be done through chemical stimulation. This is accomplished by using low doses of Kainic acid (KA), a direct agonist of the Glutamic Kainate receptors, to evoke sustained neuronal activation without causing seizures. Objective: The aim of this study is to examine the effect of AMN stimulation in modulating adult hippocampal neurogenesis at early and later stages to follow the fate of stem-progenitor cells proliferation. This study includes single as well as multiple sessions of electrical stimulation of the AMN using two types of electrodes (cupper or platinum) and chemical stimulation or continuous KA micro-perfusion of that nucleus by an implanted mini-osmotic pump. Methods: Adult Sprague-Dawle