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Is CaMKII autophosphorylation a switch to regulate memory consolidation?

Obiettivo

Understanding molecular basis of learning and memory still remains one of the more fascinating goals of neurobiology. The calcium/calmoduline kinase II (CaMKII) is one of the candidates for memory molecules. The kinase activity and function can be regulated by its autophosphorylation on threonine 286 (T286). The autophosphorylation has been shown to be essential for gene transcription and memory formation after training of contextual conditioning. The need for alphaCaMKII autophosphorylation to consolidate memory can be, however, overcome by intensive training.

The main objectives of the project are the following:
a) to test whether the autophosphorylation of alphaCaMKII regulates gene transcription which specifically contributes to memory consolidation;
b) to test which signalling cascades connect alphaCaMKII activation with consolidation-related gene-expression;
c) to investigate whether extensive training can activate alternative signalling to induce consolidation-specific transcription in the autophosphorylation-deficient mutants (T286A mice);
d) to identify brain regions where alphaCaMKII autophosphorylation contributes to gene transcription occurring during memory consolidation and thus identify brain regions which specifically contribute to memory consolidation.

Here we will establish the role of CaMKII as regulator of memory consolidation using an integrative approach: behavioural studies with T286A mutants will be combined with various molecular and biochemical analyses of gene expression and kinase activation. These studies will advance the molecular understanding of memory formation after a single episode, which is affected in many memory-related disorders such as Alzheimer and apos;s disease.

Campo scientifico (EuroSciVoc)

Parole chiave

Argomento(i)

Invito a presentare proposte

FP6-2005-MOBILITY-5
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Meccanismo di finanziamento

EIF - Marie Curie actions-Intra-European Fellowships

Coordinatore

KINGS COLLEGE LONDON
Contributo UE
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Costo totale
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