Descrizione del progetto
Una nuova interpretazione dei meccanismi alla base della reazione di attacco o fuga
Sebbene la paura e l’ansia siano spesso considerate come risposte emotive negative, esse sono essenziali per la sopravvivenza umana. La paura ci rende consapevoli delle minacce percepite o reali e ci incentiva ad agire. Il progetto PeptidesAndFear, finanziato dall’UE, indagherà i meccanismi neurobiologici alla base della cosiddetta reazione di attacco o fuga e i conseguenti adattamenti comportamentali. Iniziando dalla solida ipotesi secondo cui neuropeptidi specifici modulino i circuiti sinaptici coinvolti nello stato di paura e ansia, il progetto identificherà tali neuropeptidi. Il lavoro del progetto potrebbe svelare importanti legami tra i neuropeptidi disfunzionali e altri disturbi neuropsichiatrici.
Obiettivo
Fear and anxiety are Fear and anxiety are essential for survival. Adequate reactions to anticipated and perceived threats strongly depend on the current state, context and previous experience. What are the neurobiological mechanisms that underlie these adaptive behaviors? While synaptic circuits are the backbone to process threat signals and transform them into behavioral responses, increasing evidence suggests that neuropeptides tune these synaptic circuits in a state- and context-dependent manner, thus allowing for temporal control of excitability and plasticity. Neuropeptide receptors are abundantly expressed in neuronal circuits that regulate fear and anxiety. In fact, recent evidence suggests that most neurons synthesize multiple neuropeptides and, in turn, are regulated by multiple neuropeptide receptors that are expressed in highly cell type-specific patterns. Indeed, genetic alterations in humans as well as pharmacological and genetic experiments in mice indicate important roles for multiple neuropeptides in regulating fear and anxiety and, if dysfunctional, increasing the risk for multiple neuropsychiatric disorders. However, due to the lack of specificity of existing tools, the circuit mechanisms underlying these effects are largely unknown.
In this proposal I aim to reveal cell type-specific neuropeptidergic signaling mechanisms for context-dependent regulation of cortical circuit activity, cellular excitability and synaptic plasticity. I will use cutting-edge in vivo imaging and circuit manipulation tools combined with region- and cell type-specific CRISPR/Cas9-mediated genetic ablation to reveal how these neuropeptidergic signaling mechanisms regulate behavioral responses in the context of fear and anxiety. This multidisciplinary approach will allow me to gain unprecedented mechanistic insights into how neuropeptides drive adaptive circuit computations and how their dysfunction underlies maladaptive behavioral and emotional responses to external cues.
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Invito a presentare proposte
(si apre in una nuova finestra) ERC-2021-STG
Vedi altri progetti per questo bandoMeccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
1090 Wien
Austria