Davide Ragozzino

Laureato in Scienze Biologiche presso l’Università Tor Vergata Roma nel 1990, ha ottenuto il titolo di Dottore di ricerca in Biotecnologie presso l’Università dell’Aquila nel 1995. Attualmente ricopra la posizione di professore ordinario in Fisiologia, presso il Dipartimento di Fisiologia e Farmacologia dell’Università Sapienza di Roma. Il suo principale interesse di ricerca è indirizzato a  comprendere il contributo delle interazioni microglia-neurone alla regolazione della trasmissione sinaptica in condizioni fisiologiche e patologiche.

“Il progetto multidisciplinare mira a determinare il ruolo della microglia nel rimodellamento della trasmissione glutammatergica nel nucleus accumbens, durante l’astinenza da cocaina. Questo rimodellamento circuitale è alla base dei meccanismi che promuovono la ricaduta nell’uso di droga dopo l’astinenza forzata. Questo progetto affronta una questione di grande rilevanza sociale e clinica, esplorando i meccanismi che mantengono il desiderio persistente di farmaci e la vulnerabilità alle ricadute. Questo tema è particolarmente rilevante per la missione dell’Istituto Pasteur – Fondazione Cenci Bolognetti, di ridurre il carico di dovuto alle malattie.

Role of microglia on synaptic adaptations in the nucleus accumbens during abstinence from cocaine: from mechanisms to strategies for drug relapse prevention

Beyond their immune function, microglia have key homeostatic functions in the brain. In particular, it is now well accepted that they control the life of synapses in different contexts: from development to plasticity, and pathologies. The main objective of this proposal is to determine the role of microglia in remodeling nucleus accumbens-(NAc) glutamatergic transmission, through the maturation of newly formed silent synapses, which underlies critical circuit mechanisms promoting cocaine craving (a risk factor for drug relapse), a feature of cue-associated cocaine memories. Our central hypothesis, based on the current literature and our preliminary results (see below), is as follows: microglia neuron interactions dependent on fractalkine/CX3CR1 signaling contribute to the maturation and plasticity of silent glutamatergic synapses in the NAc, which embed critical memory traces that promote cue-induced cocaine craving. To verify this hypothesis, we will combine behavioral measures, biochemistry, whole-cell patch clamp recordings and a pharmacological intervention in mice and rats. Our proposal is based on the following 3 main aims: 1) Determine the effects of microglial depletion of glutamatergic transmission in the nucleus accumbens during forced abstinence from cocaine-induced conditioned place preference. 2) Determine the role of fractalkine/CX3CR1 signaling on the electrophysiological properties of excitatory synapses in acute slices of nucleus accumbens after forced abstinence from cocaine-induced conditioned place preference. 3) Determine the causal role of fractalkine signaling in modulating incubated cocaine craving after forced abstinence from cocaine-self administration (the gold standard procedure employed to study drug addiction-related neurobiological mechanisms). We believe that our proposal, combining behavioral, electrophysiological and biochemical approaches, will offer a completely new and promising focus to address a question of great social and clinical relevance.