Deficient Neurogenesis in Forebrain-Specific Presenilin-1 Knockout Mice Is Associated with Reduced Clearance of Hippocampal Memory Traces

To examine the in vivo function of presenilin-1 ( PS1), we selectively deleted the PS1 gene in excitatory neurons of the adult mouse forebrain. These conditional knockout mice were viable and grew normally, but they exhibited a pronounced deficiency in enrichment-induced neurogenesis in the dentate...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2001-12, Vol.32 (5), p.911-926
Main Authors: Feng, Ruiben, Rampon, Claire, Tang, Ya-Ping, Shrom, David, Jin, Janice, Kyin, Maureen, Sopher, Bryce, Martin, George M, Kim, Seong-Hun, Langdon, Ronald B, Sisodia, Sangram S, Tsien, Joe Z
Format: Article
Language:English
Subjects:
Alzheimer Disease - genetics
Amyloid beta-Protein Precursor - analogs & derivatives
Amyloid beta-Protein Precursor - metabolism
Animals
Brain Chemistry - genetics
Electrophysiology
Hippocampus - growth & development
Hippocampus - pathology
Membrane Proteins - deficiency
Membrane Proteins - genetics
Memory - physiology
Memory Disorders - genetics
Memory Disorders - pathology
Memory Disorders - physiopathology
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Mice, Transgenic
Neurons - pathology
Presenilin-1
Prosencephalon - growth & development
Prosencephalon - pathology
PS1 gene
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary:To examine the in vivo function of presenilin-1 ( PS1), we selectively deleted the PS1 gene in excitatory neurons of the adult mouse forebrain. These conditional knockout mice were viable and grew normally, but they exhibited a pronounced deficiency in enrichment-induced neurogenesis in the dentate gyrus. This reduction in neurogenesis did not result in appreciable learning deficits, indicating that addition of new neurons is not required for memory formation. However, our postlearning enrichment experiments lead us to postulate that adult dentate neurogenesis may play a role in the periodic clearance of outdated hippocampal memory traces after cortical memory consolidation, thereby ensuring that the hippocampus is continuously available to process new memories. A chronic, abnormal clearance process in the hippocampus may conceivably lead to memory disorders in the mammalian brain.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(01)00523-2