Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze

Abstract

BackgroundThe possibility of using deep brain stimulation (DBS) for memory enhancement has recently been reported, but the precise underlying mechanisms of its effects remain unknown. Our previous study suggested that spatial memory improvement by medial septum (MS)-DBS may be associated with cholinergic regulation and neurogenesis. However, the affected stage of memory could not be distinguished because the stimulation was delivered during the execution of all memory processes. Therefore, this study was performed to determine the stage of memory affected by MS-DBS. Rats were administered 192 IgG-saporin to lesion cholinergic neurons. Stimulation was delivered at different times in different groups of rats: 5 days before the Morris water maze test (pre-stimulation), 5 days during the training phase of the Morris water maze test (training-stimulation), and 2 h before the Morris water maze probe test (probe-stimulation). A fourth group of rats was lesioned but received no stimulation. These four groups were compared with a normal (control) group.ResultsThe most effective memory restoration occurred in the pre-stimulation group. Moreover, the pre-stimulation group exhibited better recall of the platform position than the other stimulation groups. An increase in the level of brain derived neurotrophic factor (BDNF) was observed in the pre-stimulation group; this increase was maintained for 1 week. However, acetylcholinesterase activity in the pre-stimulation group was not significantly different from the lesion group.ConclusionMemory impairment due to cholinergic denervation can be improved by DBS. The improvement is significantly correlated with the up-regulation of BDNF expression and neurogenesis. Based on the results of this study, the use of MS-DBS during the early stage of disease may restore spatial memory impairment.

Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model

“…Significant differences in speed were not observed among the groups, suggesting that there are no SAP-induced differences in motor function (Fig. 6e), which is consistent with our previous findings [35].…”

“…Our data support the theory that forebrain acetylcholine affects AHN, and a selective cholinergic lesion of the BFC system induces a decrease in BrdU, EGR1, DCX, and AChE levels; therefore, these findings indicate a reduction in proliferation and neuroblast production in SGZ and a decrease in hippocampal acetylcholine activity, respectively [35]. We found that the FUS-mediated BBB opening led to an increase in BDNF, EGR1, and AHN levels, which lead to an improvement in cognitive function.…”

“…The performance of all rats in all groups gradually improved across 5 days of MWM training, suggesting that rats with cholinergic dysfunction have a similar level of learning capacity and escape latency compared with wild-type rats (Fig. 6) [34, 35]. In the probe test, when compared with the control and FUS groups, the SAP group displayed a diminished MWM performance 72 h after final training, as measured by the number of crossing over the platform area and time spent, which complements the findings of previous studies [33–36, 44].…”

“…Previous studies have modeled cholinergic degeneration and cognitive function-impaired dementia in rats by intraventricularly administering the selective immunotoxin 192 IgG-saporin (SAP) to induce lesions in BFC neurons [32–35]. To investigate the effect of FUS on AHN in a cholinergic degeneration rat model of dementia, adult male Sprague Dawley rats ( n = 48; 200–250 g) were divided into control (phosphate-buffered saline [PBS] injection), SAP, and SAP+FUS groups.…”

Effects of pregabalin on neurobehavior in an adult male rat model of PTSD

“…This task is based upon the premise that animals have evolved an optimal strategy to explore their environment and escape from the water with a minimum amount of effort—i.e., swimming the shortest distance possible [29]. The time it takes a rat to find a hidden platform in a water pool after previous exposure to the setup, using only available external cues, is determined as a measure of spatial memory [30]. The water maze test, as described previously with minor modifications, was used on all animals [31, 32].…”