Thalamic Stimulation in Awake Rats Induces Neurogenesis in the Hippocampal Formation

Abstract

Background: Deep brain stimulation (DBS) provides clinical benefits for a variety of movement disorders and lately emerged as a potential treatment for cognitive and mood disorders. Modulation of adult hippocampal neurogenesis may play a role in mediating its effects.

Objective: To investigate the effects of unilateral anteromedial thalamic nucleus (AMN) stimulation on adult hippocampal neurogenesis in awake and unrestrained rats.

Methods: Four groups of adult Sprague-Dawley male and female rats received unilateral stimulation (n = 6 each) or sham surgery (n = 4 each) in the right AMN; another group of males (n = 4) was stimulated in the right ventral posterolateral thalamic nucleus (VPL). A naive group of males and females (n = 4 each) was also included. Rats received 4 injections (50 mg/kg/injection) of 5'-bromo-2'-deoxyuridine (BrdU) 3 days post-surgery and were euthanized 24 h later. The fractionator method was used together with confocal microscopy to count BrdU, GFAP and NeuN positive cells in the dentate gyrus (DG) and hilar zone of the hippocampus.

Results: Focal neurogenesis was induced in the ipsilateral DG after AMN but not VPL stimulation. Stimulation-induced effects were sex-independent and translated into a 76% increase in proliferation of neural stem/progenitor cells. Increased neurogenesis was most prominent at the caudal region of the DG, while no effect was detected in the hilar and the subventricular zones.

Conclusions: The exclusive hippocampal neurogenic response to AMN stimulation suggests an involvement of the Papez circuitry in mediating DBS effects and in the treatment of cognitive and behavioral disorders.

Keywords: Deep brain stimulation; Dentate gyrus; Hippocampus; Neurogenesis; Thalamic stimulation.