Ricerc@Sapienza

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 start elucidating the neuron-microglia signaling 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 follow: 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 propose to determine the role of fractalkine signaling in modulating incubated cocaine craving after forced abstinence from cocaine-self administration .

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.