Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons

被引:261
作者
Huerta, PT
Sun, LD
Wilson, MA
Tonegawa, S [1 ]
机构
[1] MIT, Howard Hughes Med Inst, Ctr Learning & Memory, Dept Biol, Cambridge, MA 02139 USA
[2] MIT, RIKEN MIT Neurosci Res Ctr, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0896-6273(00)80909-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In humans the hippocampus is required for episodic memory, which extends into the spatial and temporal domains. Work on the rodent hippocampus has shown that NMDA receptor (NMDAR)-mediated plasticity is essential for spatial memory. Here, we have examined whether hippocampal NMDARs are also needed for temporal memory. We applied trace fear conditioning to knockout mice lacking NMDARs only in hippocampal CA1 pyramidal cells. This paradigm requires temporal processing because the conditional and unconditional stimuli are separated by 30 s (trace). We found that knockout mice failed to memorize this association but were indistinguishable from normal animals when the trace was removed. Thus, NMDARs in CA1 are crucial for the formation of memories that associate events across time.
引用
收藏
页码:473 / 480
页数:8
相关论文
共 44 条
[11]   Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning [J].
Kim, JJ ;
Thompson, RF .
TRENDS IN NEUROSCIENCES, 1997, 20 (04) :177-181
[12]   EMOTIONAL MEMORY-SYSTEMS IN THE BRAIN [J].
LEDOUX, JE .
BEHAVIOURAL BRAIN RESEARCH, 1993, 58 (1-2) :69-79
[13]   DETERMINANTS OF NONSPATIAL WORKING-MEMORY DEFICITS IN RATS GIVEN INTRAVENTRICULAR INFUSIONS OF THE NMDA ANTAGONIST AP5 [J].
LYFORD, GL ;
GUTNIKOV, SA ;
CLARK, AM ;
RAWLINS, JNP .
NEUROPSYCHOLOGIA, 1993, 31 (10) :1079-1098
[15]   Sequence of single neuron changes in CA1 hippocampus of rabbits during acquisition of trace eyeblink conditioned responses [J].
McEchron, MD ;
Disterhoft, JF .
JOURNAL OF NEUROPHYSIOLOGY, 1997, 78 (02) :1030-1044
[16]  
McEchron MD, 1998, HIPPOCAMPUS, V8, P638, DOI 10.1002/(SICI)1098-1063(1998)8:6<638::AID-HIPO6>3.0.CO
[17]  
2-Q
[18]   Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout mice [J].
McHugh, TJ ;
Blum, KI ;
Tsien, JZ ;
Tonegawa, S ;
Wilson, MA .
CELL, 1996, 87 (07) :1339-1349
[19]   HIPPOCAMPAL SYNAPTIC ENHANCEMENT AND INFORMATION-STORAGE WITHIN A DISTRIBUTED MEMORY SYSTEM [J].
MCNAUGHTON, BL ;
MORRIS, RGM .
TRENDS IN NEUROSCIENCES, 1987, 10 (10) :408-415
[20]   HIPPOCAMPUS, TIME, AND MEMORY [J].
MECK, WH ;
CHURCH, RM ;
OLTON, DS .
BEHAVIORAL NEUROSCIENCE, 1984, 98 (01) :3-22