| Objective It has been widely confirmed that long-term aerobic exercise can improve learning and memory.However,studies have pointed out that exercise can induce the forgetting of stored memories through neurogenesis,and reduce the proactive interference of original memory traces through forgetting,thereby improving the acquisition of new memories with similar and conflict content.Are the traces of forgotten memories really gone?Does previous learning experience have a certain effect on new memory acquisition after exercise-induced forgetting?Is there any different effects of exercise on acquiring memories with different interference?What is the molecular mechanism that exercise improves learning and memory by reducing proactive interference?This study intends to explore whether the forgotten memory still has an impact on the acquisition of new memories through behavioral experiments.Secondly,the spatial memory test is used to further confirm the inhibitory effect of exercise on proactive interference,and explore the molecules mechanism that exercise reduces proactive interference.Method In order to explore whether previous learning experience still has an impact on learning of similar tasks after exercise-induced forgetting,C57BL/6J male mice were used in our study.Mice were divided into 4 groups:sedentary group without learning experience(NMT+Sed),exercise group without learning experience(NMT+Ex),sedentary group with learning experience(WMT+Sed)and exercise group with learning experience(WMT+Ex).The learning experience group received Morris water maze spatial navigation training and platform exploration test before exercise intervention to ensure that the mice obtained the spatial memory of the platform position.The learning experience group did not receive training.After the test,they were divided into different groups,exercise group engaged in 4 weeks of voluntary running,and the sedentary group was raised normally.After 4 weeks,a memory retention test was performed on the learning experience group,and 24 hours after the test,all experimental mice were subjected to post-exercise contralateral platform spatial memory training(for the experienced group,it is the reversal task training,for the inexperienced group,the test is the space Navigation training)to detect the acquisition of new spatial memory in different groups.In order to explore the inhibitory effect of exercise on proactive interference,we set up a low-interference group(new label task)and a high-interference group(reverse learning task)for learning tasks.The experiment is divided into four groups:sedentary group in low-interference(LI+Sed),exercise group in low-interference(LI+Ex),sedentary group in high-interference(HI+Sed)and exercise group in high-interference(HI+Ex).All four groups of mice received pre-exercise spatial navigation test and platform exploration test to ensure that all mice have acquired spatial memory.After the test,the mice will be given a 4-week exercise intervention(normally raised in the sedentary group)according to the group.After the intervention,a recall test will be performed to detect the memory retention of the mice.After the recall test,mice in low interference group will be accepted a spatial navigation training with new markers(that is,the markers used to identify the platform position in the water maze were completely different from those before exercise intervention).The high-interference group will received a reversal learning with reversed navigation cues.The performance was examined in the post-exercise test.In addition,we also compared the exploration of the original platform position and quadrant in the HI groups in the reversal learning task.To investigate the molecular mechanism of exercise-induced inhibition in proactive interference,we used Western blot technology to detect the protein expression of glutamate pathway in three brain regions including the hippocampus,prefrontal cortex and striatum.To further confirm the role of glutamate receptor NR2B in reducing proactive interference during exercise.We divided the mice into 4 groups:antagonist sedentary group(Sed+NR2B),antagonist exercise group(Ex+NR2B),placebo sedentary group(Sed+Nacl)and placebo exercise group(Ex+Nacl).All mice received pre-exercise spatial navigation training and platform exploration test.After the test,the mice underwent 4 weeks of voluntary wheel running or normal rearing.A recall test was performed after the 4 weeks intervention.And then all mice were engaged in a reversal learning.In the end of the probe test of reversal learning,brain tissues were taken for western blot detection.Result(1)The effect of learning experience and exercise on new memory acquisition:In the learning experience group,4 weeks of autonomous runner exercise intervention significantly reduced the retention of memory in mice;compared with the no learning experience group,the learning experience group The performance in the reversal learning task has obvious advantages,and there is no significant difference between the quiet group and the exercise group;compared with the quiet group,the exercise group uses more direct strategies when learning new tasks,and whether there is learning experience or not is for direct strategies There is no significant difference in the use of.(2)Interference conditions and the effect of exercise on new memory acquisition:In the high-interference learning task(that is,the reversal learning task),the exercise group has an obvious learning advantage over the quiet group,while this learning advantage is Elimination:During the high-interference learning process,the quiet group mice explored the position and quadrant of the original platform significantly higher than the exercise group.(3)The related molecular mechanism in similar spatial memory acquisition with exercise:In the experiment with or without learning experience,compared with the NMT group,the mice in WMT group have a significant increase in Arc,mAChR M1 and p-CaMK Ⅱ/CaMK Ⅱ in the hippocampus prefrontal cortex and striatum.Exercise increased the expression of cell membrane NR2B in the learning experience group,decreased the expression of cell membrane GluR2,and increased the expression of cytoplasmic GluR2.Exercise also increased the level of hippocampal p-GluR2 in the WMT group;exercise increased the level of The expression of TARP and Arc in the hippocampus of the WMT group.(4)The related molecular mechanism in reducing proactive interference with exercise:In the experiment 5,when compared with the low-interference group,the mAChR M1,Arc,CaMK Ⅱ and p-CaMK/CaMK Ⅱ in the high-interference group were significantly increased in the hippocampus prefrontal cortex and striatum.Under high-interference conditions,exercise was significant Increased the level of hippocampus NR2B and p-GluR2/GluR2,as well as the expression of TARP and Arc.In experiment 6,the results showed that NR2B antagonist injection eliminates exercise to reverse learning tasks The promotion effect of NR2B antagonist is related to that NR2B antagonist reduces the inhibition of proactive interference by exercise.NR2B antagonist reduces the phosphorylation level of hippocampal GluR2 in the exercise group.Conclusion(1)Long-term voluntary exercise can promote the forgetting of information related to specific markers in spatial memory,thereby inhibiting the proactive interference of original memory traces on new memories when they acquire similar memories.(2)The forgetting-promoting effect of exercise does not affect the retention of indirect exploration strategies that are not related to specific markers.The reserved indirect exploration strategies can further promote the acquisition of similar memories.(3)Exercise promotes the endocytosis of GluR2 by increasing the expression of NR2B in the cell membrane of the hippocampus,thereby promoting the inhibition of proactive interference.(4)The upstream regulatory factors of GluR2,mAChR M1 and CaMK Ⅱ,may be involved in the regulation of proactive interference in high-interference memory tasks,but they are not regulated by exercise. |
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