Dynamic activity patterns and cortico-subcortical interactions in the human brain

openQuesto progetto di tesi si propone di indagare la natura della connettività funzionale dinamica (dFC), con un particolare focus sulle sue basi neurali e sulla sua possibile rilevanza comportamentale. Nello specifico, partendo da uno studio pubblicato nel 2022 da Favaretto e colleghi, valuteremo il ruolo delle comunicazioni cortico-sottocorticali nella modellazione della dFC, nonché l'importanza dei suoi parametri nel predire specifici aspetti demografici e comportamentali.This thesis project aims at broadly investigating the nature of dynamic funtctional connectivity (dFC), with a specific focus on its neural underpinnings and potential behavioral relevance. In particular, leading from a study published in 2022 by Favaretto and collegues, we will assess the role of cortico-subcortical communications in shaping dFC as well as the influence of dFC metrics on demographic traits and individual behavior

Serotonin depletion causes valproate-responsive manic-like condition and increased hippocampal neuroplasticity that are reversed by stress

Abnormal hippocampal neural plasticity has been implicated in behavioural abnormalities and complex neuropsychiatric conditions, including bipolar disorder (BD). However, the determinants of this neural alteration remain unknown. This work tests the hypothesis that the neurotransmitter serotonin (5-HT) is a key determinant of hippocampal neuroplasticity, and its absence leads to maladaptive behaviour relevant for BD. Depletion of brain 5-HT in Tph2 mutant mice resulted in reduced behavioural despair, reduced anxiety, marked aggression and lower habituation in novel environments, reminiscent of bipolar-associated manic behaviour. Treatment with valproate produced a substantial improvement of the mania-like behavioural phenotypes displayed by Tph2 mutants. Brain-wide fMRI mapping in mutants revealed functional hippocampal hyperactivity in which we also observed dramatically increased neuroplasticity. Importantly, remarkable correspondence between the transcriptomic profile of the Tph2 mutant hippocampus and neurons from bipolar disorder patients was observed. Chronic stress reversed the emotional phenotype and the hippocampal transcriptional landscape of Tph2 mutants. These changes were associated with inappropriate activation of transcriptional adaptive response to stress as assessed by gene set enrichment analyses in the hippocampus of Tph2 mutant mice. These findings delineate 5-HT as a critical determinant in BD associated maladaptive emotional responses and aberrant hippocampal neuroplasticity, and support the use of Tph2-/- mice as a new research tool for mechanistic and therapeutic research in bipolar disorder