Deep Brain Stimulation of the Nucleus Basalis of Meynert in an Experimental Rat Model of Dementia: Stimulation Parameters and Mechanisms.

Background/objective: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has gained interest as a potential therapy for treatment-resistant dementia. However, optimal stimulation parameters and mechanisms of action are yet to be elucidated. Methods: First, we assessed NBM DBS at different stimulation parameters in a scopolamine-induced rat model of dementia. Rats were tested in the object location task with the following conditions: (i) low and high frequency (20 Hz or 120 Hz), (ii) monophasic or biphasic pulse shape (iii) continuous or intermittent DBS (20s on, 40s off) and 100 mu A amplitude. Thereafter, rats were stimulated with the most effective parameter followed by 5-bromo-2 '-deoxyuridine (BrdU) administration and perfused 4 weeks later. We then evaluated the effects of NBM DBS on hippocampal neurogenesis, synaptic plasticity, and on cholinergic fibres in the perirhinal and cingulate cortex using immunohistochemistry. We also performed in-vivo microdialysis to assess circuit-wide effects of NBM DBS on hippocampal acetylcholine levels during on and off stimulation. Results: Biphasic, low frequency and intermittent NBM DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that acute stimulation promoted proliferation in the dentate gyrus, increased synaptic plasticity in the CA1 and CA3 subregion of the hippocampus, and increased length of cholinergic fibres in the cingulate gyrus. There was no difference regarding hippocampal acetylcholine levels between the groups. Conclusion: These findings suggest that the potential mechanism of action of the induced memory enhancement through NBM DBS might be due to selective neuroplastic and neurochemical changes.