Project description DEENESFRITPL A new interpretation of the mechanisms behind the fight-or-flight response While fear and anxiety are usually regarded as negative emotional responses, they are essential to human survival. Fear makes us aware of perceived or real threats and motivates us to take action. The EU-funded PeptidesAndFear project will investigate the neurobiological mechanisms behind this so-called fight-or-flight response and the ensuing behavioural adaptations. Beginning from the strong hypothesis that specific neuropeptides modulate the synaptic circuits involved in states of fear and anxiety, the project will identify these neuropeptides. The project’s work might unravel important links between dysfunctional neuropeptides and other neuropsychiatric disorders. Show the project objective Hide the project objective Objective 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. Fields of science natural sciencesbiological sciencesneurobiologycognitive neurosciencesocial sciencespsychologycognitive psychology Keywords Neuropeptides prefrontal cortex CRISPR Cas9 G protein signaling fear and anxiety GABAergic neurons ion channels synapses neuronal activity plasticity Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2021-STG - ERC STARTING GRANTS Call for proposal ERC-2021-STG See other projects for this call Funding Scheme HORIZON-ERC - HORIZON ERC Grants Host institution MEDIZINISCHE UNIVERSITAET WIEN Net EU contribution € 1 499 725,00 Address SPITALGASSE 23 1090 Wien Austria See on map Region Ostösterreich Wien Wien Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 725,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MEDIZINISCHE UNIVERSITAET WIEN Austria Net EU contribution € 1 499 725,00 Address SPITALGASSE 23 1090 Wien See on map Region Ostösterreich Wien Wien Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 725,00
