GIGA - Annual report 2023

research 58 research 59 LAURENT NGUYEN Deciphering species-specific mechanisms of neuron migration Cerebral cortex morphogenesis relies on an exquisite choreography of neural cells that migrate together in shared forebrain area. The project NEUREVODEVO builds upon solid preliminary comparative analyses made across three mammalian species which revealed species-specific patterns of cIN migration. Here, we will consolidate these observations by time-lapse microscopy and further combine single cell analyses with functional experiments to decipher the molecular machinery responsible for singularities in cIN migration in the different species. Our work will shed light on novel evo-devo mechanisms that control cell movement. Furthermore, our pioneer pipeline may help designing better human-based models for drug screening against neurodevelopmental disorders associated with neuron migration defects for which, according to our preliminary data, mouse models might not be ideal. CHRISTINA SCHMIDT Impact of insomnia on emotional responses and its cerebral correlates In the last few years insomnia disorder (ID) has been attracting inscreasing attention due to its huge socioeconomic burden, its prevalence and destructive impact on mental health. Altered emotion regulation may not only result from ID but also constitutes a risk factor for its development. However, a consensus about ID-related alteration in the functional brain circuitry underlying emotion regulation has not yet been reached, putatively due to heterogeneity in the expression and development of the disease. Furthermore, whether and how ID affects sleep-dependent overnight emotional adaptation remains underexplored, even though ID has been suggested to go along with restless rapid eye movement (REM) sleep, which appears crucial for such adaptive response. In this study, we will assess behavioural and cerebral responses to emotional stimuli in homogenous samples of ID patients based on a recently suggested ID subtyping. Contrary to previous studies that predominantly assessed the instant brain activation underlying emotion regulation by using a regional cortical approach, we will use magnetic resonance imaging (MRI) to probe ID-related differences in functional connectivity of emotional brain responses and the implication of the arousal and REM sleep regulating subcortical locus coeruleus (LC). We will further assess the impact of ID on the overnight adaptive response in the salience network and limbic circuit. We expect decreased activation, altered functional connectivity and less efficient overnight adaptation to emotional distress in ID. We finally hypothesize that these differences will be associated with the degree of electrophysiology-derived REM sleep consolidation, and are mediated by structural and functional LC integrity. The study will provide new evidence on the detrimental impact of restless REM sleep on ID expression and contribute to the understanding of emotion regulation as a mechanism underlying ID.

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