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Decoding neuropeptide function in inhibitory amygdala microcircuits

Project description

The role of neuropeptides in adaptive behaviour

Accumulating evidence indicates that various psychiatric conditions involve maladaptive learning processes. Neuropeptides known to help neuronal communication and plasticity, especially under stress, are thought to play a key role in this. However, their precise function in brain circuits remains poorly understood. The ERC-funded DecodeNP project aims to uncover how neuropeptides affect fear and anxiety. The research team will focus on specialised neurons in the amygdala, the part of the brain deeply involved in processing emotions. Using advanced imaging and molecular profiling, they will study exactly when neuropeptides are released and how they influence neural activity. Ultimately, the project hopes to shed light on the biological mechanisms behind survival-related behaviour and help understand how anxiety disorders develop.

Objective

Adaptive behaviour to ever-changing environments is crucial for an animal’s survival in conditions of immediate threat. Meanwhile, there is growing evidence that psychiatric conditions, including anxiety disorders, are at least partly based on maladaptive learning. Neuropeptide signalling plays a key role in regulating synaptic plasticity and hence learning in a state-dependent manner, and dysregulated peptide signalling has been observed in patients suffering from psychiatric disorders. Due to specific expression of peptides and their receptors in distinct cell types and microcircuits, they can contribute to the specificity of neural communication on both temporal and spatial scales. However, the signalling mechanisms and behavioural roles of neuropeptides in individual circuit elements are not well understood.
In this proposal, we will use a multimodal approach to determine the role of neuropeptides in innate and learned fear and anxiety states. We will focus on microcircuits of the amygdala, more specifically on distinct interneuron types, which co-release different peptides with their common main transmitter GABA. Using state-of-the-art technology, we will analyse under which conditions neuropeptides are released from interneurons, and probe their causal contribution to fear learning and anxiety states with intersectional genetic interrogations. Large-scale, longitudinal in vivo calcium imaging combined with novel spatial transcriptomics will further reveal peptide impact on circuit computations. As both amygdala circuitry and function as well as neuropeptide expression are evolutionarily conserved, we expect that this proposal will unravel fundamental mechanisms of neural circuit functions for survival. This research will not only provide novel insights into the neural mechanisms of fear and anxiety, but will also hold significant clinical relevance for understanding the underlying pathophysiological processes that contribute to psychiatric disorders.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2024-COG

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Host institution

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Net EU contribution
€ 1 999 621,00
Address
VENUSBERG-CAMPUS 1/99
53127 Bonn
Germany
Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost
€ 1 999 621,00

Beneficiaries (1)