Restorative Plasticity At Corticostriatal Excitatory Synapses (REPLACES)

REPLACES focused on the molecular and biological mechanisms underlying brain plasticity and repair that may occur in neurodegenerative diseases, that range among the most costly brain disorders in Europe. Alteration of brain plasticity may lead to the motor and functional disturbances observed in neurodegenerative diseases. Therapeutic approaches targeting brain and synaptic plasticity could prevent neuronal degeneration and restore altered motor and cognitive functions. The two „classic‟ forms of long-term synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), are occur at most excitatory synapses throughout the brain and have both been described at corticostriatal connections, at which they might underlie motor-skill learning, cognitive performance and reward mechanisms. The induction of synaptic plasticity in the striatum requires interaction between dopamine (DA) and glutamate receptors. A unique feature of corticostriatal plasticity is the observation that the loss of both these opposite forms of synaptic plasticity has been found in experimental models of Parkinson‟s disease (PD), a neurodegenerative disorder caused by the selective loss of dopaminergic nigrostriatal neuronal projections. Thus indicating experimental models of parkinsonisms as a paradigmatic model “par excellence” where to study brain plasticity and approaches to unravel neurodegeneration and repair. The REPLACES project has be focused on studying brain plasticity and repair in physiological and pathological conditions, i.e. experimental PD, using cortical striatal plasticity as paradigmatic model.


4.219.766,00 €.

Project Duration 
Novembre 2008 – Ottobre 2012.

Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano - Coordinatore

Leibniz-Institut für Neurobiologie, Magdeburg (Germania)

INSERM - Université Pierre et Marie Curie, Paris (Francia)

School of Bioscences, Cardiff University (Regno Unito)

Wallenberg Neuroscience Center, Lund University (Svezia)

Sobell Department Institute of Neurology, UCL - University College London (Regno Unito)

CNRS - Centre National de la Recherche Scientifique, Montpellier (Francia)