Showing papers by "Susumu Tonegawa published in 2002"
TL;DR: Results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall by generating and analyzing a genetically engineered mouse strain in which the N-methyl-d-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice.
Abstract: Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by generating and analyzing a genetically engineered mouse strain in which the N-methyl-D-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice. The mutant mice normally acquired and retrieved spatial reference memory in the Morris water maze, but they were impaired in retrieving this memory when presented with a fraction of the original cues. Similarly, hippocampal CA1 pyramidal cells in mutant mice displayed normal place-related activity in a full-cue environment but showed a reduction in activity upon partial cue removal. These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall.
1,064 citations
TL;DR: With its combinatorial property, this binary recombination‐activated neuronal marker system should facilitate the study of detailed morphology, connectivity, and plasticity of defined classes of live neurons in vitro and in vivo.
Abstract: A new strategy for visualizing neuronal cell morphology of mouse brain based on Cre/loxP recombination-activated gene expression is described. A "reporter" transgenic line was generated which expressed a fusion gene encoding a dendrite-targeted green fluorescent protein (MAP2-GFP) upon deletion of a transcription/translation STOP (transcription and translation stop signal) cassette. Cre transgenic "deleter" lines were established that activated reporter gene expression at various frequencies in pyramidal neurons in the forebrain. A deleter line was identified which activated a MAP2-GFP reporter gene at very low frequency (less than 0.1% of pyramidal neurons) and allowed the visualization of dendritic structures of individual neocortical and hippocampal pyramidal neurons. In addition, vertical "columns" of pyramidal neurons in the neocortex were labeled in these mice. In a second deleter line, a MAP2-GFP reporter gene was selectively activated in pyramidal neurons of the CA-1 subregion of the hippocampus in young mice. With its combinatorial property, this binary recombination-activated neuronal marker system should facilitate the study of detailed morphology, connectivity, and plasticity of defined classes of live neurons in vitro and in vivo.
11 citations