Role of fractalkine on synaptic adaptations in the nucleus accumbens during abstinence from cocaine

Anno
2021
Proponente Ingrid Reverte Soler - Ricercatore
Sottosettore ERC del proponente del progetto
LS5_1
Componenti gruppo di ricerca
Componente Categoria
Davide Antonio Ragozzino Aggiungi Tutor di riferimento (Professore o Ricercatore afferente allo stesso Dipartimento del Proponente)
Abstract

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.

ERC
LS5_6, LS6_3
Keywords:
NEUROSCIENZE COMPORTAMENTALI, NEUROFISIOLOGIA, NEUROFARMACOLOGIA, TOSSICOLOGIA

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