Project description
Understanding abnormal processing of sensory information
During preadolescence, abnormal sensory information processing (SIP) can potentially lead to mental disorders, especially in males. The exact role of hyperdopaminergia in SIP deficits remains unexplored, as does why it is more prevalent in males and how it contributes to mental disorders. The ERC-funded REDIRECT project will leverage a rodent model of prenatal cannabis exposure to address these issues. Researchers will use molecular interrogation to examine factors that promote resilience and prevent hyperdopaminergia and SIP deficits in females. The project’s goal is to gain insights into how sex influences genes, circuits, and behaviour, ultimately leading to the development of personalised therapies for SIP deficits.
Objective
Mental disorders are associated with abnormal sensory information processing (SIP) at preadolescence, especially in males. Aberrant SIP is a neutral cross-disorder trait that can be translated between humans and animals and assessed as the inability to prevent/gate an overload of irrelevant information. The mechanisms underlying physiological and pathological SIP variability are unexplored. Particularly, the causative role of hyperdopaminergia, key to SIP deficits, has never been tested by isolating, spatially and temporally, this single neural component. How does this trait evolve into a mental disorder? Why does it occur more often in males?
REDIRECT will capitalize on our rodent model of prenatal cannabis exposure (PCE), which is the first of its kind to offer, at preadolescence, a sex bias in susceptibility to SIP deficits upon acute exposure to stress or cannabis. This animal model is amenable to molecular interrogation to probe causality for those resilience-promoting factors preventing females from developing a hyperdopaminergia and SIP deficits.
By combining viral strategies to trace and probe cell-type specific input-output reorganization of dopamine circuits (Aim 1), with single-cell transcriptome analyses (Aim 2), REDIRECT will decipher how female sex imposes distinct molecular changes to neurons and circuits, which are key to prevent the etiopathogenesis of SIP disorders. By testing selected candidate genes to probe causality for how sex modulates genes, developmental trajectories, and behaviour, we will decode (Aim 3) how discrete dopaminergic circuits can be reprogrammed sex-dependently.
REDIRECT will causally disentangle how sex differently affects genes, circuits, and behaviour to inform novel sex-specific and age-tailored therapies for SIP deficits, a cross-disorder trait typical of common and severe mental illnesses, including autism, attention deficit hyperactivity disorder, obsessive-compulsive disorder and schizophrenia
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.
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Programme(s)
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2022-COG
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09124 CAGLIARI
Italy
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