The effects of electrical stimulation of the nucleus basalis magnocellularis/the reuniens thalamic nucleus on memory function in a rat model of dementia

Abstract

Deep brain stimulation has been used to treat various neurological disorders. Recently, some studies suggest that deep brain stimulation can treat Alzheimer’s disease. Memory deficits associated with a reduction in cholinergic projections in the cortex and hippocampus are the one of the characteristics of Alzheimer’s disease. This study was designed to determine the effect of electrical stimulation of the nucleus basalis magnocellularis or the reuniens thalamic nucleus on spatial memory using a rat model mimicking the basal forebrain cholinergic deficits of Alzheimer’s disease. We damaged basal forebrain cholinergic neurons using 192 IgG-saporin. Rats in the stimulation group received stimulation of the nucleus basalis magnocellularis and the reuniens thalamic nucleus daily beginning one week after surgery until the start of behavioral testing. The Morris water maze and the object in place were used to evaluate visuo-spatial and visuo-working memory 2 weeks after surgery. Choline acetyltransferase immunohistochemistry was performed to examine 192 igG-saporin-induced cholinergic lesions in the medial septum, and acetylcholinesterase assay was used to evaluate acetylcholinesterase activity in the medial prefrontal cortex and hippocampus. Also, we used western blot analysis to examine changes in GABAergic and glutamatergic systems. The stimulation group of the nucleus basalis magnocellularis showed excellent performance in the probe trial of the Morris water maze task. In the stimulation group of the nucleus basalis magnocellularis, the reduction of the glutamate and glutamic acid decarboxylase was induced in the medial prefrontal cortex. The stimulation group of the reuniens thalamic nucleus showed slightly higher performance in the object in place task. In the stimulation group of the reuniens thalamic nucleus, the reduction of the glutamate in the medial prefrontal cortex and glutamic acid decarboxylase in the hippocampus was induced. Also, the acetylcholinesterase activity was significantly increased as compared to the implantation group of the reuniens thalamic nucleus. The present study demonstrates that stimulation of the nucleus basalis magnocellularis appears to predominately facilitate visuo-spatial memory, whereas stimulation of the reuniens thalamic nucleus appears to predominately facilitate visuo-working memory.