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REVIEW: NEUROSCIENCE Memory—a Century of Consolidation James L. McGaugh The memory consolidation hypothesis proposed 100 years ago by Mu ¨ller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over the century in understanding the time- dependent processes that create our lasting memories. A century has passed since Mu ¨ller and Pilzecker proposed the perseveration- consolidation hypothesis of memory ( 1 ). In pioneering studies with human sub- jects, they found that memory of newly learned information was disrupted by the learning of other information shortly after the original learning and suggested that processes underlying new memories initially persist in a fragile state and consolidate over time. At the beginning of this new millennium, the con- solidation hypothesis still guides research in- vestigating the time-dependent involvement of neural systems and cellular processes en- abling lasting memory ( 2–4 ). Retrograde Amnesia and Memory Enhancement Clinical evidence that cerebral trauma induc- es loss of recent memory was reported two decades before the publication of Mu ¨ller and Pilzecker’s monograph, and shortly after its publication, it was noted that the consolida- tion hypothesis provided an explanation for such retrograde amnesia ( 5 ). Ignored for al- most half a century, the consolidation hy- pothesis was reinvigorated in 1949, when two papers reported that electroconvulsive shock induced retrograde amnesia in rodents ( 6, 7 ), triggering a burst of studies of experimentally induced retrograde amnesia ( 2–4 ). That same year, Hebb and Gerard proposed dual-trace theories of memory, suggesting that the sta- bilization of reverberating neural activity un- derlying short-term memory produces long- term memory ( 7, 8 ). The finding that protein synthesis inhibitors did not prevent the learn- ing of tasks but disrupted memory of the training ( 9 ) supports the view that there are (at least) two stages of memory and indicates that protein synthesis is required only for consolidation of long-term memory. The is- sue of whether short- and long-term memory (and, perhaps, other memory stages) (Fig. 1) are sequentially linked, as proposed by Hebb and Gerard, or act independently in parallel ( 3, 10 ) remains central to current inquiry. The discovery that stimulant drugs administered within minutes or hours after training en- hance memory consolidation further stimulat- ed studies of memory consolidation ( 3, 10 , 11 ). The use of treatments administered shortly after training to impair or enhance memory provides a highly effective and ex- tensively used method of influencing memo- ry consolidation without affecting either ac- quisition or memory retrieval ( 11 ). Endogenous Modulation of
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This note was uploaded on 08/12/2008 for the course PSY 332 taught by Professor Salinas during the Fall '07 term at University of Texas at Austin.

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