Neurophysiology and Plasticity Lab

Areas of Investigation 

The Laboratory of Neurophysiology and Plasticity studies the pathophysiology of the basal ganglia, with special focus on the striatum, in genetic models of movement disorders such as Parkinson's disease and dystonia. The Laboratory uses biochemical, immunohistochemical, molecular and electrophysiological techniques to identify alterations of molecular mechanisms that may be among the causes of the characteristic neurological deficits of these disorders.

Parkinson's disease is caused by the degeneration of dopaminergic neurons, which leads to an altered function of the basal ganglia circuit. The identification of mutations responsible for familial forms of the disease have made it possible to generate genetic models, essential for the characterization of the pathogenic mechanisms leading to the striatal dysfunction. In particular, the activity of the Laboratory research has allowed to describe the significant alterations in corticostriatal synaptic plasticity in a genetic model of monogenic autosomal recessive parkinsonism, caused by mutations in the PINK1 gene. Our current studies aim to identify the pathophysiological mechanisms underlying the striatal synaptic plasticity changes in PINK1parkinsonism.

The Laboratory research also focuses on primary dystonia. It is a relatively common chronic disorder of the movement, whose symptoms often appear in early childhood. Today there are limited treatment options available. DYT1 dystonia is the most common inherited form, caused by an autosomal dominant mutation (deletion DGAG) in TOR1A gene. In our studies we described how this mutation is able to alter the striatal physiology and we are currently working to characterize the underlying pathophysiological mechanism.

 

Applied Methodologies

The Laboratory of Neurophysiology and Plasticity is equipped with systems for electrophysiological recordings “in vitro”. Applied techniques range from conventional to those of more recent introduction. The electrophysiological recording in patch-clamp mode is associated with a simultaneous measurement of intracellular ion levels, as well as optogenetics stimulation. Additionally techniques for imaging of ions and techniques of molecular biology, immunohistochemistry and stereotactic injections of viral vectors are used. The Laboratory relies on the close interaction with the group of researchers led by Prof. Antonio Pisani in the Department of Systems Medicine of Tor Vergata University of Rome.

Collaborations 
  • Ceinge - Advanced Biotechnologies, Naples (Italy)
  • Department of Neurobiology, The University of Alabama, Birmingham (United States)
  • Department of Neurology, University of Perugia (Italy)
  • Department of Systems Medicine, Tor Vergata University of Rome (Italy)
  • Institut des Maladies Neurodégénératives (IMN), Bordeaux (France)
  • Institut für Medizinische Genetik und angewandte Genomik, Tübingen (Germany)
  • Laboratory of Behavioral Neurobiology, Sapienza – University of Rome (Italy)
  • Laboratory of Molecular Neurobiology, Harvard Medical School, Boston (United States)
  • Neuroscience Laboratory, Department of Systems Medicine, Tor Vergata University of Rome (Italy)
  • Unit of Molecular and Functional Neurogenetics, CSS Mendel Institute, Rome (Italy)
  • Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University, Nashville (United States)
  • VIB Center for the Biology of Disease, KU Louvain (Belgium)
Ongoing Research Projects 
  • Ripristino della funzione colinergica nella distonia DYT1
  • Nuovo approccio di normalizzazione della trasduzione del segnale del recettore della dopamina D2 in un modello sperimentale di distonia DYT1
  • Nuove strategie neuroprotettive per la malattia di Parkinson: ruolo di PINK1 nella regolazione di autofagia e apoptosi
  • Analisi optogenetica delle connessioni Striatum-Globus pallidus in un modello di distonia DYT1

Laboratory of Neurophysiology and Plasticity

Fondazione Santa Lucia Irccs

Via del Fosso di Fiorano, 64 00143 Rome

European Centre for Brain Research (CERC) – Floor 2 – Room 203, 205, 315