NR1基因敲除对小鼠前额叶脑区LTP的影响

华东师范大学学报(自然科学版) ›› 2012, Vol. 2012 ›› Issue (1): 47-53.

NR1基因敲除对小鼠前额叶脑区LTP的影响

杨李果，曾庆文，张旭亮，曹晓华

华东师范大学脑功能基因组学教育部重点实验室，上海市脑功能基因组学重点实验室，上海 200062

收稿日期:2011-02-01 修回日期:2011-05-01 出版日期:2012-01-25 发布日期:2012-01-26

Long-term potentiation of prefrontal cortex in NR1 knockout mice

YANG Li-guo, ZENG Qing-wen, ZHANG Xu-liang, CAO Xiao-hua

Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China

Received:2011-02-01 Revised:2011-05-01 Online:2012-01-25 Published:2012-01-26

摘要/Abstract

摘要： 用前脑特异性NR1基因敲除小鼠，采用离体脑片场电位技术，研究了NR1亚基在前额叶脑区突触可塑性中的作用.刺激强度—反应(input-output curve)和双脉冲抑制反应(paired pulse depression, PPD)的结果表明，与同窝对照组小鼠相比，NR1基因敲除小鼠前额叶脑区的基本突触传递无明显变化.采用高频刺激(100 Hz, 1 000 ms ×2, 间隔30 s)在小鼠的前额叶脑区诱导长时程增强(long-term potentiation, LTP)，与对照组小鼠相比，NR1基因敲除小鼠前额叶脑区的LTP明显受损.以上数据提示，NR1亚基在前额叶脑区LTP的诱导中起着重要的作用.

关键词: N-甲基-D-天门冬氨酸受体, 前额叶皮层, 长时程增强

Abstract: This study investigated the prefrontal synaptic plasticity of forebrain-specific NR1 knockout mice by using the vitro field potential recording technique. The results from the input-output and paired pulse depression curves suggest that the basal synaptic transmission is normal in the prefrontal cortex of NR1 knockout mice. Prefrontal long-term potentiation (LTP) induced by high frequency stimulation (two trains of 100 Hz with 1 s duration and 30 s interval) was abolished in slices of NR1 knockout mice. These results indicate that NR1 is critical in the induction of long-term potentiation in prefrontal cortex.

Key words: N-methyl-D-aspartic acid receptor, prefrontal cortex, long-term potentiation

中图分类号:

Q189

杨李果，曾庆文，张旭亮，曹晓华. NR1基因敲除对小鼠前额叶脑区LTP的影响[J]. 华东师范大学学报(自然科学版), 2012, 2012(1): 47-53.

YANG Li-guo, ZENG Qing-wen, ZHANG Xu-liang, CAO Xiao-hua. Long-term potentiation of prefrontal cortex in NR1 knockout mice[J]. Journal of East China Normal University(Natural Sc, 2012, 2012(1): 47-53.

参考文献

［1］BLISS T V, COLLINGRIDGE G L. A synaptic model of memory: long-term potentiation in the hippocampus［J］. Nature, 1993, 361: 31-39.

［2］MALENKA R C, NICOLL R A. NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms［J］. Trends Neurosci, 1993, 16: 521-527.

［3］BEAR M F, MALENKA R C. Synaptic plasticity: LTP and LTD［J］. Curr Opin Neurobiol, 1994(4): 389-399.

［4］NAKANISH S. Molecular diversity of glutamate receptors and implications for brain function［J］. Science, 1992, 258: 597-603.

［5］HOLLMANN M, HEINEMANN S. Cloned glutamate receptors［J］. Annu Rev Neurosci, 1994, 17: 31-108.

［6］SHENG M, CUMMINGS J, ROLDAN L A, et al. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex［J］. Nature, 1994, 368: 144-147.

［7］TSIEN J Z, HUERTA P T, TONEGAWA S. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory［J］. Cell, 1996, 87: 1327-1338.

［8］CUI Z, WANG H, TAN Y, et al. Inducible and reversible NR1 knockout reveals crucial role of the NMDA receptor in preserving remote memories in the brain［J］. Neuron, 2004, 41: 781-793.

［9］TANG Y P, SHIMIZU E, DUBE G R, et al. Genetic enhancement of learning and memory in mice［J］. Nature, 1999, 401: 63-69.

［10］ ROBBINS T W. From arousal to cognition: the integrative position of the prefrontal cortex［J］. Prog Brain Res, 2000, 126: 469-483.

［11］ GOTO Y, YANG C R, OTANI S. Functional and dysfunctional synaptic plasticity in prefrontal cortex: roles in psychiatric disorders［J］. Biol Psychiatry, 2010, 67: 199-207.

［12］ MATSUDA Y, MARZO A, OTANI S. The presence of background dopamine signal converts long-term synaptic depression to potentiation in rat prefrontal cortex［J］. J Neurosci, 2006, 26: 4803-4810.

［13］ ZHAO M G, TOYODA H, LEE Y S, et al. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory［J］. Neuron, 2005, 47: 859-872.

［14］ DEBNNE D, GUERINEAU N C, GAHWILER B H, et al. Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release［J］. J Physiol, 1996, 491 (Pt 1): 163-176.

［15］ NICOLL R A, MALENKA R C. Contrasting properties of two forms of long-term potentiation in the hippocampus［J］. Nature, 1995, 377: 115-118.

［16］ DURAND G M, KOVALCHUK Y, KONNERTH A. Long-term potentiation and functional synapse induction in developing hippocampus［J］. Nature, 1996, 381: 71-75.

［17］ HIRSCH J C, CREPEL F. Postsynaptic calcium is necessary for the induction of LTP and LTD of monosynaptic EPSPs in prefrontal neurons: an in vitro study in the rat［J］. Synapse, 1992(10): 173-175.

［18］ WATANABE M, KODAMA T, HIKOSAKA K. Increase of extracellular dopamine in primate prefrontal cortex during a working memory task［J］. J Neurophysiol, 1997, 78: 2795-2798.

［19］ COURTNEY S M. Attention and cognitive control as emergent properties of information representation in working memory［J］. Cogn Affect Behav Neurosci, 2004(4): 501-516.［20］ MATSUO K, GLAHN D C, PELUSO M A, et al. Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder［J］. Mol Psychiatry, 2007(12): 158-166.

［21］ FUSTER J M. The prefrontal cortex-an update: time is of the essence［J］. Neuron, 2001, 30: 319-333.

［22］ WILKINS A J, SHALLICE T, MCCARTHY R. Frontal lesions and sustained attention［J］. Neuropsychologia, 1987, 25: 359-365.

［23］ ROSSI S, CAPPA S F, BABILONI C, et al. Prefrontal ［correction of Prefontal］ cortex in long-term memory: an “interference” approach using magnetic stimulation［J］. Nat Neurosci, 2001(4): 948-952.

［24］ HERRY C, GARCIA R. Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice［J］. J Neurosci, 2002, 22: 577-583.

［25］ EGERTON A, REID L, MCKERCHAR C E, et al. Impairment in perceptual attentional set-shifting following PCP administration: a rodent model of set-shifting deficits in schizophrenia［J］. Psychopharmacology (Berl), 2005, 179: 77-84.

［26］ KOCERHA J, FAGHIHI M A, LOPEZ-TOLEDANO M A, et al. MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction［J］. Proc Natl Acad Sci USA, 2009, 106: 3507-3512.