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Title: Analysis of memory consolidation and reconsolidation in the mouse hippocampus
Author: von Hertzen, Laura Sisko Johanna
ISNI:       0000 0001 3549 095X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2005
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Our brain processes enormous amounts of information subserving the formation and retrieval of memory. A fresh memory is an unstable trace that is stabilised by a process termed consolidation. This depends on de novo transcription. Reactivating a stabilised memory returns it to a labile state, and triggers a second consolidation process, termed reconsolidation, re-stabilising the memory again. This study used two transcriptional screens to determine the molecular relationship between consolidation and reconsolidation. Three immediate-early genes were identified to be regulated in the hippocampus after contextual fear conditioning in the mouse: Serum and Glucocorticoid regulated Kinase 1 (SGKl), SGK3 and Nerve Growth Factor Inducible gene B (NGFI-B). The up-regulation of SGKl expression was triggered by the environment, and thus SGK-1 might be important for the formation of a contextual representation. The up- regulation of SGK3 and NGFI-B expression was specific to the context-shock association, suggesting a role for these genes in the consolidation of the context-shock association. Re-exposure of the mice to the context reiterated the upregulation of SGKl and SGK3 expression, demonstrating that some transcriptional events after contextual conditioning are recapitulated during reconsolidation, and showing for the first time that an expression change specific to the context-shock association (SGK3) can be subsequently recapitulated during reconsolidation. It was also established that the transcriptional changes induced by retrieval depended on the remoteness of the reactivated memory. In contrast to SGKl and SGK3, NGFI-B was not regulated during reconsolidation, and therefore was specific to memory consolidation. This consolidation-specific regulation of NGFI-B was confined to hippocampal area CAl and required ?CaMKll autophosphorylation. This finding suggests a link between synaptic activity and gene regulation in memory formation. Functional studies of NGFI-B showed that NGFI-B was important for hippocampus-dependent memory formation. The discovery of this consolidation-specific transcript indicates that reconsolidation is only a partial recapitulation of consolidation at the transcriptional level.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available