Ziel
"In recent years significant progress has been made into deciphering the initial triggering mechanisms responsible for the induction of synaptic strengthening. Contrarily, very few studies address the question as to which cellular processes are responsible for the maintenance of LTP. Recently, the protein kinase M zeta (PKMζ, an atypical protein kinase C) has taken center stage in the field of synaptic plasticity due to its unique role in the maintenance of LTP. Among some of the most crucial observations are: 1) the increased in PKMζ mRNA level following LTP5, 2) Its protein product is constitutively active, 3) postsynaptic perfusion of PKMζ alone increases synaptic strength, 4) it is necessary and sufficient for the maintenance of LTP. Furthermore, its inhibition reverses pre-established LTP and most importantly erases memories. Therefore this protein merits a primary role in the maintenance of memory traces.
Although PKMζ activity is crucial for the persistence of LTP however little is known about its precise cellular and molecular mechanisms of action. Recent evidence point to its role in the rapid redistribution of preexisting surface receptors on the plasma membrane. For example, pharmacologically blocking postsynaptic exocytosis with Botulinum toxin B fails to disrupt PKMζ-induced synaptic potentiation. Meanwhile the same manipulation leads to rapid and persistent rundown of synaptic transmission. Provided that blocking exocytosis is not involved in the PKMζ-mediated effects on synaptic transmission leads me to hypothesize that PKMζ must regulates surface diffusion of AMPARs either by trapping at the postsynaptic density or reshuffling of AMPARs from extrasynaptic to synaptic sites. In this proposal I will test this using a combination of high resolution imaging techniques, molecular biology and electrophysiology."
Wissenschaftliches Gebiet
Aufforderung zur Vorschlagseinreichung
FP7-PEOPLE-2010-IIF
Andere Projekte für diesen Aufruf anzeigen
Finanzierungsplan
MC-IIF - International Incoming Fellowships (IIF)Koordinator
75794 Paris
Frankreich