Project description
Genetic and environmental controls on the development of emotional circuits
Neuronal circuits associated with the amygdala are essential to emotional regulation and control anxiety levels, fear and stress responses. These circuits develop and mature after birth and are sensitive to the environment. Early-life stress such as that induced by mother-offspring separation can impact the maturation of brain circuits with lasting impact on emotional regulation and anxiety, but the underlying molecular and cellular mechanisms are unknown. The ERC-funded EmoDevo project seeks to investigate the development of amygdala circuits, focusing on the regulatory role of transcriptional programmes and the influence of early-life stress. For this reason, the team will use transcriptomics, axon tracings, CRISPR-Cas9-mediated gene manipulation together with maternal separation during development and anxiety and emotional memory tests in adults.
Objective
Emotion regulation and responses to fear and stress are vital for survival and interactions with the environment. Within the brain, the amygdala governs emotional states through specialised nuclei and connectivity, controlling anxiety, fear reactions, and emotional learning.
In mammals, amygdala circuits mature postnatally and are influenced by mother-offspring bonding, which impairment causes early-life stress and leads to lasting consequences on anxiety. However, the molecular and cellular mechanisms underlying amygdala neuron differentiation and wiring, their reliance on intrinsic programs, potential sex differences, and impact of early-life experiences remain poorly understood.
Here, I hypothesise that the differentiation of amygdala neurons relies on transcriptional programs, which vary between sexes and are modulated by early-life stress. Building on advanced technologies and expertise for single-cell gene expression, spatial position and connectivity analyses, that I developed in my prior work, I propose to test this in the amygdalae of female and male mice, by:
1. Identifying transcriptional programs guiding neuron differentiation using single-nucleus and spatial transcriptomics.
2. Characterizing projection development and intrinsic programs using barcoded axon tracings combined with transcriptomics.
3. Determining the role of intrinsic determinants and the impact of early-life stress on projection development and function using CRISPR-Cas9-mediated gene manipulation, maternal separation, 3D axon tracings, and anxiety/emotional memory tests.
These experiments will reveal transcriptional programs governing amygdala circuit development and sex dimorphisms. They will identify amygdala neuron types sensitive to environment, potentially more prone to be affected in diseases. This research will contribute to understanding the genetic and environmental aspects of emotional dysregulation, a common feature in neuropsychiatric disorders, including anxiety disorders.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been validated by the project's team.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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(opens in new window) ERC-2024-STG
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9052 ZWIJNAARDE - GENT
Belgium
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