Thalamic stimulation in awake rats induces neurogenesis in the hippocampal formation -

Abstract

Background and Aims: Deep brain stimulation has the potential to provide substantial clinical benefits for a variety of movement disorders, and is currently under investigation for the treatment of cognitive disorders. However, the molecular mechanisms mediating these effects remain elusive. One possible underlying mechanism might be the regulation of adult hippocampal neurogenesis. The present study investigates the effects of unilateral anteromedial thalamic nucleus stimulation on adult hippocampal neurogenesis in awake and unrestrained rats. Methods: Our study was based on the following 5 experimental groups. Group 1: adult female rats (n=4) were subjected to unilateral stimulation in the right anteromedial thalamic nucleus (AMN). Group 2: adult male rats (n=6) received unilateral stimulation in the right AMN. Group 3: adult female (n=2) and male (n=4) sham rats were subjected to electrode implantation only without current delivery. Group 4: adult male rats (n=2) received unilateral stimulation in the right ventral posterolateral thalamic nucleus. Group 5: adult female rats (n=3) received a single injection of KA (500pM) in the right AMN. All rats, except those in group 5, received 4 injections (50mg-Kg-injection) of 5’-bromo-2’-deoxyuridine (BrdU) 3 days after surgery and euthanized 24 h later. Rats in group 5 received single injection of BrdU (50mg-kg) for 5 days and were euthanized 3 h after the last injection. Confocal immunofluorescent analysis of BrdU, GFAP and NeuN was performed. Stereological counting of positive cells was done in the dentate gyrus and hilar zone of the hippocampal formation, using the fractionator method. Results: Stimulation of the right AMN induced focal neurogenesis in the ipsilateral (right) dentate gyrus. Stimulation-induced effects were gender-independent and were translated by an increase in prolifereation rate at the level of amplifying neural progenitors. Importantly, increased-neurogenesis rate was limited to the caudal region of the dentate gyrus. Furthermore