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

NR1基因敲除对小鼠前额叶脑区LTP的影响

1.
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

详细信息

中图分类号: Q189
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出版历程
- 收稿日期: 2011-02-01
- 修回日期: 2011-05-01
- 刊出日期: 2012-01-25

Long-term potentiation of prefrontal cortex in NR1 knockout mice

1.
Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China

摘要

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.
- 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.
- N-methyl-D-aspartic acid receptor /
- prefrontal cortex /
- long-term potentiation

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参考文献(1)

[1]

［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.

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