Synaptic Plasticity And Learning Memory Of Prefrontal Cortex And DG In βCaMKⅡ-F90G Transgenic Mice

Learning and memory,as high function of brain,are critical for mammalian survival and other behaviors.Many researches indicate that prefrontal cortex(PFC) is important for the working memory,emotion memory,attention regulation and behavior inhibition in human and rodents.N- methyl- D- aspartate receptor(NMDAr),a ligand-gated ion channel,plays a crucial role in synaptic plasticity,learning and memory of PFC. Ca²⁺/calmodulin-dependent protein kinaseâ…¡(CaMKâ…¡) is an important downstream molecule of NMDAr.When NMDAr opens,Ca²⁺ inflow into the postsynaptic membrane, and activate CaMKâ…¡,which is interactive with the NR2B subunit,and then modulate both of synaptic plasticity and the ability of learning and memory.CaMKâ…¡is consisted ofαandβsubunit in brain.There are a lot of researches aboutαsubunit,but seldom onβsubunit.Some studies show that the function of CaMKâ…¡depends on the ratio ofα:β.We use the protein modified transgenic mice(Tg) to study the effect of overexpressionβCaMKâ…¡on working memory.This study includes four parts:1.genotype analysis and functionalβCaMKâ…¡-F90G expressionThe SV40 primers were designed to cloneβCaMKâ…¡gene of genomic DNA isolated from mice tails for genotype analysis.Western-blot strategy was applied to identify the expression ofβCaMKâ…¡gene.Data show that the functionalβCaMKâ…¡is overexpressed in the synapse of prefrontal cortex in transgenic mice.2.The basic and emotional behavior ofβCaMKâ…¡-F90G transgenic miceFirst,some basic behavioral tasks such as open field,rotard test,dark and light box test and elevated plus maze were used to study the basic activity and emotional behavor inβCaMKâ…¡-F90G transgenic mice.No significant difference has been observed in the locomotor activity,exploration,emotion and innate fear between transgenic mice and wild type mice(Wt). 3.The spacial working memory inβCaMKâ…¡-F90G transgenic miceIt has been reported that overexpressionβCaMKâ…¡in dentate gyrus reduces the synaptic plasticity and impairs the memory consolidation.To investigate the relationship between overexpression ofβCaMKâ…¡in prefrontal cortex and prefrontal cortex dependent working memory function,we use T-maze DNMS(the delayed non match-to-sample) and modified water maze tasks to study the spatial working memory in mice.The results show that the transgenic mice have normal spatial working memory,which indicate that the overexpression ofβCaMKâ…¡in prefrontal cortex may not influence the spatial working memory in mice.4.The synaptic transmission inβCaMKâ…¡-F90G transgenic miceWe investigate the effect ofβCaMKâ…¡overexpression specific in forebrain on synaptic plasticity in dentate gyrus.The data show that the LTD of transgenic mice is significantly decreased than that of wild type.The results indicate that overexpression ofβCaMKâ…¡subunit may weaken the LTD.