Thalamic Stimulation in Awake Rats Induces Neurogenesis in the Hippocampal Formation

- Basal and specific gender-dependent neurogenesis has been observed in naive adult rats.
- Unilateral electrical stimulation of the anteromedial thalamic nucleus increased neurogenesis in awake rats.
- Increased neurogenesis was ipsilateral to stimulation and showed spatial preference.
- Anteromedial thalamic nucleus stimulation was specific to the dentate gyrus of the hippocampus.
- Comparable stimulation to other sensory thalamic nuclei failed to alter basal hippocampal neurogenesis.

BackgroundDeep 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.ObjectiveTo investigate the effects of unilateral anteromedial thalamic nucleus (AMN) stimulation on adult hippocampal neurogenesis in awake and unrestrained rats.MethodsFour 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.ResultsFocal 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.ConclusionsThe 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.