Project description
Illness may help reveal the function of brain enigma in health
Scientists have made tremendous progress over several centuries in identifying distinct anatomical regions of the brain and associating them with specific functions. But the claustrum remains a sort of black box. First identified in the late 1600s and found only in mammals, we now know that it receives input from nearly every area of the cortex and projects back to almost all of them. However, what occurs between input and output remains a mystery. The claustrum is the brain structure with the highest levels of an opioid receptor for the most powerful hallucinogenic in nature. In the mouse brain, it expresses many genes associated with elevated risk for schizophrenia, characterised in part by hallucinations. The EU-funded CLAUSTROFUNCT project is following this lead, investigating the claustrum's role in healthy brains and determining whether disrupting its function can cause symptoms of schizophrenia.
Objective
Schizophrenia is a chronic mental disease having an incidence of 1% worldwide. Its symptoms are numerous and range from hallucinations to altered executive functions. Although the exact causes of schizophrenia are unknown, several works suggest that impaired communication between higher cortical centers may be important for the expression of the disease. Establishing a causal link between circuit function (and/or dysfunction) and particular behavioral traits relevant to schizophrenia may shed new light on the mechanisms underlying the pathology.
Dysfunction of the prefrontal cortex (PFC) may contribute to cognitive deficits relevant to schizophrenia. In a search for circuits potentially regulating the PFC, we identified an enigmatic and not well-studied network, the claustrum (CLA). This subcortical structure of unknown function is supposed to be highly reciprocally interconnected with the neocortex, especially associative cortices involved in behavioral traits relevant to schizophrenia. It is thus uniquely positioned to influence cortical communication. The CLA is also peculiar because it represents the brain structure expressing the highest levels of kappa opioid receptor, the receptor of the most potent hallucinogenic drug found in nature, salvinorin A, suggesting a potential role played by the CLA in hallucinations. This link is further supported by medical reports in which patients having transient or permanent lesions in the claustrum develop hallucinations and delusions concomitantly. Finally, many risk factors genes associated to schizophrenia are strongly and often selectively expressed in the mouse claustrum.
In summary, this combination of evidences led us to hypothesize that the claustrum may represent a circuit whose malfunction is relevant to the expression of schizophrenia. Our proposal will test the role of the claustrum in the normal brain and test whether its dysfunction may contribute to schizophrenia symptoms.
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Funding Scheme
ERC-SyG - Synergy grantHost institution
1211 Geneve
Switzerland