GABAergic interneurons of the mammalian cerebral cortex display a variety of morphological and physiological behaviors that are thought to be crucial for both the development and the function of mature cortical circuits. Defects in cortical inhibition have been implicated in neurological and psychiatric disorders such as epilepsy, depression, anxiety, addiction, schizophrenia and autistic disorders. Research over the past decade has shown a common embryonic origin for most mouse cortical interneurons in the ganglionic eminences (ventral regions) of the telencephalon, from where they tangentially migrate to reach the cortex. Within the cortex, interneurons integrate into the local circuitry while they develop mature and distinct morphological and physiological properties. To achieve specific functions, different interneuron subtypes have to growth and pattern cell-type-specific dendrite and axon arborizations, and establish specific patterns of synaptic connections. The genetic programs that control the differentiation of distinct interneuron subtypes in the developing cerebral cortex are largely unknown. This proposal is aimed to understand how regulatory networks of transcription factors acting during the prolonged period of cortical interneuron differentiation, from progenitors in the ganglionic eminences to mature cortical interneurons, specify distinct cell fates. In particular, we will use in vitro (RNA interference) and in vivo (mouse models) approaches to understand the regulation and maintenance of terminal interneuron differentiation, including the pattern and growth of axonal arborizations. These studies will help to elucidate the mechanisms that regulate the development and function of the cerebral cortex in normal and pathological conditions.
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