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Optimization Of Interneuron Function By Direct Coupling Of Cell Migration And Axonal Targeting Pdf

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Published: 25.03.2021

Lynette Lim , Janelle M. Pakan, Martijn M.

A small subset of interneurons that are generated earliest as pioneer neurons are the first cohort of neurons that enter the neocortex.

Early-generated interneurons regulate neuronal circuit formation during early postnatal development

SHANK2 is a scaffold protein that serves as a protein anchor at the postsynaptic density in neurons. Genetic variants of SHANK2 are strongly associated with synaptic dysfunction and the pathophysiology of autism spectrum disorder. Recent studies indicate that early neuronal developmental defects play a role in the pathogenesis of autism spectrum disorder, and that insulin-like growth factor 1 has a positive effect on neurite development. To investigate the effects of SHANK2 knockdown on early neuronal development, we generated a sparse culture system using human induced pluripotent stem cells, which then differentiated into neural progenitor cells after 3—14 days in culture, and which were dissociated into single neurons. Control neurons were infected with scrambled shControl lentivirus carrying a red fluorescent protein reporter shControl group. Neuronal somata and neurites were reconstructed based on the lentiviral red fluorescent protein signal. Furthermore, dendritic length and arborization were significantly increased after insulin-like growth factor 1 treatment of shSHANK2 neurons, while cell soma speed remained unaffected.

Neurodevelopmental disorders NDDs , including intellectual disability ID and autism spectrum disorders ASD , are a large group of disorders in which early insults during brain development result in a wide and heterogeneous spectrum of clinical diagnoses. Mutations in genes coding for chromatin remodelers are overrepresented in NDD cohorts, pointing towards epigenetics as a convergent pathogenic pathway between these disorders. In this review we detail the role of NDD-associated chromatin remodelers during the developmental continuum of progenitor expansion, differentiation, cell-type specification, migration and maturation. We discuss how defects in chromatin remodelling during these early developmental time points compound over time and result in impaired brain circuit establishment. In particular, we focus on their role in the three largest cell populations: glutamatergic neurons, GABAergic neurons, and glia cells. An in-depth understanding of the spatiotemporal role of chromatin remodelers during neurodevelopment can contribute to the identification of molecular targets for treatment strategies. A mature brain is the product of its development.

Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. View on Springer. Save to Library.

Optimization of interneuron function by direct coupling of cell migration and axonal targeting

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex.

A small subset of interneurons that are generated earliest as pioneer neurons are the first cohort of neurons that enter the neocortex. However, it remains largely unclear whether these early-generated interneurons EGIns predominantly regulate neocortical circuit formation. Using inducible genetic fate mapping to selectively label EGIns and pseudo-random interneurons pRIns , we found that EGIns exhibited more mature electrophysiological and morphological properties and higher synaptic connectivity than pRIns in the somatosensory cortex at early postnatal stages. In addition, when stimulating one cell, the proportion of EGIns that influence spontaneous network synchronization is significantly higher than that of pRIns. Importantly, toxin-mediated ablation of EGIns after birth significantly reduce spontaneous network synchronization and decrease inhibitory synaptic formation during the first postnatal week. A key feature of these interneurons is the incredibly rich diversity in their morphology, biochemical marker expression, electrophysiological properties and synaptic connectivity patterns Ascoli et al.

Lynette Lim, Janelle M. Optimization of interneuron function by direct coupling of cell migration and axonal targeting. T1 - Optimization of interneuron function by direct coupling of cell migration and axonal targeting. N2 - Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex.

Early-generated interneurons regulate neuronal circuit formation during early postnatal development

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