Studies On Synaptic Plasticity In Medial Prefrontal Cortex And Learning Memory Of NR2B Transgenic Rats

The medial prefrontal cortex participates in several advanced brain functions including working memory, emotional memory and selective attention. The long-term potentiation (LTP) and long-term depression (LTD) in glutamatergic synapses are thought to be the cellular mechanisms of learning and memory. The N-methyl-D-aspartate (NMDA) receptors, one of the most important glutamatergic receptors, have been proved playing an important role in synaptic plasticity as well as learning and memory. NR2B subunits which are highly expressed in the cortex, hippocampus and olfactory bulb, are one of the key subunits of NMDA receptors. Many studies have demonstrated that NR2B subunits are critical in synaptic plasticity and learning memory in the hippocampus. However, fewer studies focused on the synaptic plasticity and related functions of medial prefrontal cortex. At present, little studies can be found about the effect on the synaptic plasticity and learning memory by up-regulation of NR2B expression. Here, we employed field potential recording technique as well as behavioral methods, and investigated synaptic plasticity and related functions of the medial prefrontal cortex. The major findings of the study are showed as follows:1. Analysis of basal synaptic transmission in prelimbic cortex (PRL) of mPFC in NR2B transgenic rats.The function of basal synaptic transmission in pyramidal neurons in layerⅡto layerⅤpathway in prelimbic cortex containing slices of NR2B transgenic rats and wild type rats was investigated with field potential recording technique. Transgenic and wild type rats slices showed no significant difference in fEPSP amplitude in the input-output curve and paired-pulse ratio (PPR), suggesting that the function of AMPA receptors (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, AMPA) in the PRL and the release of neurotransmitter were not affected in the forebrain selective NR2B overexpression transgenic rats.2. Long-term potentiation (LTP) and long-term depression (LTD) in PRL of mPFC of NR2B transgenic rats.We compared the LTP between the NR2B transgenic rats and wild type rats with field potential recording technique, and no significant difference was found. However, transgenic rats exhibited more depression of LTD after 1Hz low frequency stimulation compared with wild type rats. And with 3Hz low frequency stimulation, facilitation but not LTD was found in transgenic slices while LTD existed in wild type slices. These results indicate that NR2B overexpression may not participate in the regulation of LTP formation but do depress LTD in PRL of mPFC and might lower the threshold of LTD/LTP.3. Learning and memory of NR2B transgenic rats in prefrontal-related behavioral tasksTo investigate whether the NR2B gene overexpression affect learning and memory in prefrontal cortex related behavioral tasks in NR2B transgenic rats, the open field, effort-based decision making T-maze task, delayed non-matched to sample with objects and spatial working memory task were taken. Results showed higher percent correct for NR2B transgenic rats in the high reward arm (HR arm) reverse test in effort-based decision making T-maze task compared with wild type rats, but no significant differences were found in open field, delayed non-match to sample with objects and spatial working memory task between the two groups, indicating NR2B transgenic rats have better learning flexibility.In conclusion, NR2B transgenic rats can be induced more depressed LTD in vitro, and have better performance in the HR arm reverse test in effort-based decision making T-maze task, suggesting LTD to be the mechanism of learning flexibility at cellular level, and adding new evidence for learning flexibility study. Besides, the data from 3Hz low frequency stimulation support the hypothesis that NR2A/NR2B ratio controls the LTD/LTP threshold.