Experimental Neurology Lab | Fondazione Santa Lucia

Experimental Neurology Lab

Areas of Investigation 

The Laboratory of Experimental Neurology mainly examines experimental models of various neurological diseases, such as Parkinson's and Alzheimer's diseases, as well as, amyotrophic lateral sclerosis (ALS).

The studies on Parkinson's disease (PD) are directed towards understanding the mechanisms underlying the progressive degeneration of the dopaminergic midbrain neuronal population. This degeneration is the main histopathological hallmark characterizing PD. The Laboratory also studies the functional responses of dopaminergic cell population, in order to understand the consequences of their degeneration in the all circuitry of the basal ganglia.

With respect to Alzheimer's disease, the experimental analysis of the laboratory is focused on studying cellular and molecular mechanisms underlying dysfunction of cortical and hippocampal synaptic plasticity. These have been related to the typical cognitive deficits characterizing this disease of aging.

The studies on amyotrophic lateral sclerosis (ALS) focus on elucidating the cellular and molecular mechanisms that determine the degeneration of spinal motor neurons. The loss of these neurons is correlated to the progressive impairment  of motor function in people with ALS. In the field of neurodegeneration, the Lab undertakes also research on molecules, which could be able to prevent or slow down the degeneration of neurons.

 

Preparation of Brain Slices and Electrophysiological Techniques

The dopaminergic system is studied by the Laboratory of Experimental Neurology not only in relation to Parkinson's disease, but also in the field of psychiatric disorders. These psychiatric alterations are schizophrenia, addictions, depression and attention-deficit/hyperactivity disorder. The methods primarily involve the use of electrophysiological techniques on brain slices, kept viable with perfusion of artificial cerebrospinal fluid.

These in vitro preparations are used to perform whole-cell patch-clamp recordings from single neurons. Neuronal visualization with infrared microscopy allows the recording of ionic currents that are present in the plasmalemmal membrane of cells. The Laboratory uses electrical amplifiers to obtain recordings with the method of current clamp (this establish the activity of the cells, the membrane potential and resistance), and  voltage clamp (the membrane potential is fixed at a constant value and membrane currents are measured). It is also possible to evaluate somato-dendritic currents caused by the application putative neurotransmitters, as well as, spontaneous evoked synaptic responses. The latter are usually caused by the stimulation of afferent pathways. By using microfluorimetric measurements it is also possible to detect changes in intracellular free calcium and/or sodium concentrations .

The electrophysiological analysis also includes the study neuronal activity in slice preparations by using an extracellular recording system with multi-electrode. This is constituted by grids (8x8) of 64 planar electrodes, which allow simultaneous evaluation of the electrical response in a  cellular populations, their functional connectivity and the spatial-temporal dynamics of their activity. The electrophysiological analysis, is often associated to a neurochemical evaluation of the release of the neurotransmitter dopamine in the projection structures of midbrain dopaminergic cells, utilizing amperometric techniques in slice preparations. Similar experiments are usually performed in cortical, hippocampal and striatal neurons.

Collaborations 
  • Campus Bio-Medico University of Rome (Italy)
  • Department of Neuroscience, Karolinska Institutet (Sweden)
  • Faculty of Medical Science, Univesity of Auckland (New Zealand)
  • Tor Vergata University of Rome (Italy)
  • University II of Naples (Italy)
  • University of Perugia (Italy)

Laboratory of Experimental Neurology

Fondazione Santa Lucia Irccs

Via del Fosso di Fiorano, 64 00143 Rome

European Centre for Brain Research (CERC) – Floor 2 – Rooms 206, 211, 213, 215