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Ricardo Brambilla"Complexity of striatum-dependent behavioural plasticity as revealed by genetic dissection of the Ras-ERK-CREB signalling pathway"

Abstract :

Inhibition of the Ras-ERK-CREB pathway in the CNS affects neuronal cell signalling, synaptic plasticity and memory formation.
We have shown that the striatum is particularly sensitive genetic manipulations in this pathway, affecting both long-term memory in stimulus response learning (instrumental conditioning and habit formation) and drug-related learning. However, the behavioural output of bidirectional manipulations of the Ras/ERK pathway in the brain is not entirely predictable, but rather highly dependent on the specific element of the cascade, the cell type and the local network targeted. The non linear dynamic nature of these cell signalling alterations, both at the quantitative level (stimulus intensity and duration) and qualitative one (differential cellular targets, differential activation of local networks), may be the major determinant of the systemic process underlying behavioural plasticity.

Selected publications

C. Vantaggiato, I. Formentini, A. Bondanza, C. Bonini, L. Naldini and R. Brambilla. ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially. J. Biol. (2006), 5:14.

C. Pittenger, S. Fasano, D. Mazzocchi-Jones, S.B. Dunnett, E. R. Kandel and R. Brambilla. Impaired bidirectional synaptic plasticity and procedural memory formation in striatum-specific CREB-deficient mice. J Neurosci. (2006), 26, 2808-2813.
Ferguson, S. M., Fasano, S., Yang, P., Brambilla, R., and Robinson, T. E. Knockout of ERK1 MAPK enhances cocaine-evoked immediate early gene expression and behavioural plasticity. Neuropsychopharmacology, 2006 Jan 11; [Epub ahead of print] PMID: 16407894

Erwan Bezard