Memory Enhancing Effect after Medial Septum Stimulation is Associated with Changes in Hippocampal Cholinergic and Gabaergic Activity
Journal Title: The 1st Annual Meeting of Georgian Center for Neuroscience Research - Year 2020, Vol 2, Issue 20
Abstract
Many brain disorders cause impairments in learning and memory. These include developmental disorders, as well as diseases of old age such as Alzheimer’s disease. People with these disorders often show changes in the hippocampus. One way to restore the hippocampal activity is through a technique called deep brain stimulation (DBS). But exactly how DBS restores hippocampal circuit function is unclear. The medial septum (MS) is an important modulator of hippocampal function. It has been reported that DBS of MS restores spatial memory after damage to cholinergic neurons and this effect is associated with an increase in hippocampal cholinergic activity. Our study designed to quantify the effects of implantation of electrodes or MS DBS-induced changes in hippocampal dependent spatial memory function and changes in neurotransmitters markers in the hippocampus. We utilized three groups of adult male rats: normal (control), MS electrode implantation without stimulation (sham) and MS electrode implantation and stimulation. In the chronic DBS experiment, animals received stimulation 2 hr daily for a period of 2 weeks. Learning process and long-term spatial memory were assessed using a Morris water maze; the test was divided into the training phase (days 1 - 4) and the retrieval phase. The results showed that implantation of electrodes did not prevent learning of a platform location. During the probe test which was performed 1 hour after task acquisition trained rats of all groups did not differ significantly among each other, but in marked contrast from rats of control and stimulation groups, rats of electrode implantation exhibited a retention deficit 3 days later after training. These findings demonstrate that MS electrode implantation causes impairment of hippocampal dependent long-term spatial memory and MS DBS prevent this deficit. Using immunohistochemical approaches, we found that implantation of electrodes reduced the number of parvalbum inimmunoreactive MS neurons by 30% and the number of cholinacetyltranspherase immunoreactive neurons by 23% vs. control group. Our results showed that implantation of electrodes into the MS causes in hippocampal CA1 and CA3 fields significant decrease in number of AChE-sensitive neurons, but number of immunostained GABAA receptors was significantly higher in sham group as compared to control group; in MS stimulation group number of AChE-sensitive neurons and GABAA receptors in the hippocampus was not different from the control group. Taking into account the results of our behavioral and immunohistochemical experiments it can be assumed that the cholinergic and GABAergic deficiency after implantation of electrodes is compensated by stimulation of survivor MS neurons. Our results revealed that DBS of MS facilitated long-term spatial memory and for the first time demonstrate that this effect is associated with a modulation not only of hippocampal cholinergic activity, but is paralleled with significant changes in GABAergic activity. (Supported by the funding from the SRNSFG: Grant # - FR-18-11783.)
Authors and Affiliations
M. Burjanadze, G. Beselia, T. Naneishvili, M. Dashniani
Keywords
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- EP ID EP677934
- DOI 10.29088/GCNR-2020.25
- Views 236
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