(SS#VII) Philip L. Gildenberg Resident Award (2023 Award Winner): Long Term Effects of Deep Brain Stimulation of Nucleus Basalis of Meynert in a Rat Dementia Model

Introduction: Deep brain stimulation (DBS) of the Nucleus Basalis of Meynert (NBM) is being explored for the treatment of dementia. Its role in cognition and memory has been well studied with brief durations of stimulation. More recently, Liu et al 2017 found evidence for a benefit of stimulation that persisted after the end of stimulation in 2 primates. Our laboratory has identified 5 hrs. of daily stimulation as providing maximal learning improvement as compared with 1 and 24 hours. This study explores the long-term effects of NBM DBS by assessing the rats at weekly intervals for 6 weeks after the end of stimulation.

Methods: Eighteen Long Evans wild-type male rats were divided into three groups: healthy, demented, and demented with stimulation. A memory impaired rat model that mimics cholinergic denervation of dementia was created with bilateral 192-IgG-saporin injections into the NBM to induce apoptosis of the cholinergic population. A monopolar DBS electrode was implanted in the NBM and the stimulated rats underwent a total of 50 hours of stimulation over a 2 week period. During the stimulation phase and weekly for 6 weeks afterwards, the rats were tested on an audio-cue based learning paradigm in an operant chamber.

Results: Normal rats demonstrated improvement in accuracy over time (8.39%), whereas the demented rats showed significantly less improvement (1.82%). Stimulated rats demonstrated accuracy improvement that was significantly better than unstimulated demented rats, exceeding normal rats (10.5%, all p< 0.05) as well. After the end of stimulation the stimulated rats returned to the same level of accuracy improvement as normal rats but not the demented rats.

Conclusion : NBM-DBS in a rat dementia model shows improvement in learning during stimulation that exceeds normal rats. After the end of stimulation, this returns to normal but not demented levels of accuracy improvement.