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Cellular and molecular mechanisms controlling the integration of CGE interneurons into cortical circuits

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The origin of neuron circuits in the brain

Understanding how neuronal circuits determine brain function remains one of the biggest challenges of neuroscience. A European study dissected the mechanisms by which cell layers emerge in the cerebral cortex.

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The outer part of the brain, the cerebral cortex, is responsible for many functions such as memory, attention and language. The neuronal circuits within the cerebral cortex consist of excitatory glutamatergic pyramidal cells and inhibitory interneurons. Interneuron deficits seem to underlie a variety of neurodevelopmental and psychiatric disorders, but existing knowledge of the mechanisms controlling their precise integration into cortical circuits remains limited. The EU-funded INTRACORT (Cellular and molecular mechanisms controlling the integration of CGE interneurons into cortical circuits) project determined the mechanisms mediating the allocation of interneurons into circuits in the cerebral cortex. Researchers focused on the caudal ganglionic eminence (CGE), an embryonic cortical structure that guides neuronal migration at different time points during development. Early born CGE interneurons populated deep layers of the cortex whereas interneurons emerging after E15.5 which is after the first post-natal week, demonstrated a preference for superficial cortical layers. To test if medial ganglionic eminence (MGE) interneurons influenced the location of CGE interneurons, scientists studied mice with defects in MGE interneurons. They observed that aberrant development of MGE interneurons increased CGE interneuron levels in deep layers. In another part of the project, research focused on a subtype of CGE interneurons identified through vasoactive intestinal peptide (VIP) expression. To identify the mechanism by which these cells are layered in the cortex, scientists isolated these cells at different postnatal stages and performed gene expression profiling. The selection of key genes in this process is ongoing. Taken together, these experiments will allow the dissection of the mechanisms underlying the precise integration of CGE interneurons into cortical circuits. Considering the contribution of these interneurons in the aetiology of several neurodevelopmental and psychiatric disorders, INTRACORT information has important clinical implications. Understanding the aetiology behind these disorders should fuel studies on novel therapeutic interventions.


Cerebral cortex, interneuron, INTRACORT, caudal ganglionic eminence, VIP

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