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Mapping of Italian research excellence in Neurodegenerative - Apre

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Nome Antonio Malgaroli, Gian Giacomo Consalez<br />

Contatti<br />

02 2643 4886<br />

antonio.malgaroli@hsr.it, giacomo.consalez@hsr.it<br />

Istituto/Dipartimento Università Vita-Salute San Raffaele<br />

Proposta di ricerca Optical And Biomolecular Methods For The Functional Investigation Of Neural Circuits In Vivo.<br />

Area di <strong>in</strong>teresse identificata Analisi della funzione s<strong>in</strong>aptica nei tessuti nervosi normali e <strong>in</strong> modelli di<br />

neurodegenerazione<br />

F<strong>in</strong>anziamenti ricevuti<br />

Titolo progetto<br />

Ente f<strong>in</strong>anziatore<br />

Durata progetto<br />

Optical And Biomolecular Methods For The Functional Investigation Of Neural<br />

Circuits In Vivo.<br />

Fondazione CARIPLO (pend<strong>in</strong>g)<br />

2 anni<br />

Every human behavior depends on an activity change <strong>in</strong> one or more bra<strong>in</strong> areas,<br />

<strong>of</strong>ten with the contribution <strong>of</strong> very small subgroups <strong>of</strong> cells and synapses.<br />

Conversely, when a bra<strong>in</strong> disease whatsoever, a tumor, a vascular disorder, a<br />

grey or white matter pathology, etc., modifies some behavioral aspect, <strong>in</strong>evitably<br />

this effect arises from a change <strong>in</strong> neural activity. Hence, view<strong>in</strong>g the f<strong>in</strong>e<br />

structure <strong>of</strong> the bra<strong>in</strong> by the most advanced imag<strong>in</strong>g techniques is certa<strong>in</strong>ly<br />

important but it would be more important to f<strong>in</strong>d some effective way to detect<br />

changes <strong>in</strong> neuronal and synaptic activity dur<strong>in</strong>g both physiological and<br />

pathological processes. Indeed, for many different body organs, the kidney, the<br />

heart, the liver, the pancreas, etc, the early detection <strong>of</strong> signs and symptomsand<br />

the choice <strong>of</strong> an optimized therapeutic approach <strong>of</strong>ten depend more on the<br />

availability <strong>of</strong> a large set <strong>of</strong> chemical and molecular markers <strong>of</strong> cell function<br />

rather than on our ability to visualize f<strong>in</strong>e details <strong>of</strong> the tissue anatomy.<br />

Unfortunately techniques available today to monitor bra<strong>in</strong> function, such as<br />

E.E.G., fMRI, fNIRS, etc., either sample bra<strong>in</strong> activity very <strong>in</strong>directly, through<br />

changes <strong>in</strong> metabolism and blood flow, or do not have the resolution required to<br />

p<strong>in</strong>po<strong>in</strong>t changes <strong>in</strong> small networks <strong>of</strong> neuronal cells and synapses. At present,<br />

anomalous states <strong>of</strong> bra<strong>in</strong> activity can be detected only when they arise from<br />

the concerted activity <strong>of</strong> large numbers <strong>of</strong> neurons and synapses, such as <strong>in</strong><br />

epilepsy, or when cell and/or synaptic and/or axonal damage becomes very<br />

pr<strong>of</strong>ound. For all the above reasons, the demand for a methodology that could<br />

yield a more direct readout <strong>of</strong> <strong>in</strong> vivo neuronal and synaptic activity is extremely<br />

high.<br />

In this <strong>research</strong> project we are plann<strong>in</strong>g to further develop a methodology that<br />

was recently designed <strong>in</strong> one <strong>of</strong> our labs to provide a very direct and sensitive<br />

readout <strong>of</strong> bra<strong>in</strong> activity. This is based on a family <strong>of</strong> recomb<strong>in</strong>ant molecules<br />

which were designed <strong>in</strong> our labs to detect synaptic activaton via the application<br />

<strong>of</strong> exogenous markers. This methodology is capable <strong>of</strong> reveal<strong>in</strong>g the physiological<br />

activation <strong>of</strong> bra<strong>in</strong> synaptic networks with very high sensitivity and resolution.<br />

These strik<strong>in</strong>g results have prompted the generation <strong>of</strong> a series <strong>of</strong> transgenic

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