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The coordination and role of activity in developing neural circuits

Abstract

The stereotyped synaptic connections that define neural circuit function are established during development. Neuronal activity independent of environmental stimulus contributes to neural circuit assembly in vertebrates, but its precise role remains an open question, particularly at the level of defined cell types. By contrast, invertebrate neurodevelopment was thought to proceed in the absence of such developmental activity. Here I show that developmental activity accompanies synaptogenesis in the Drosophila brain. Using Drosophila genetics, epifluorescence microscopy, two-photon microscopy, immunohistochemistry, and visual behavior, I characterize this developmental activity, determine its role in synapse formation, and identify regulatory mechanisms at the cellular and molecular level. This patterned-stimulus independent neural activity occurs in a brain-wide fashion, and is characterized by stereotyped oscillations and cellular dynamics that reflect synaptic connectivity. Activity patterns instruct synapse development in a cell-type-specific manner. A transient and genetically specified population of neurons propagates this activity throughout the brain. Glia participate with complementary cycles of activity in a cell-type-specific fashion, and astrocytes are necessary for activity to occur. These data indicate that developmental activity is an evolutionarily conserved and fundamental component of neural circuit assembly that is coordinated by multiple molecular and cellular mechanisms.

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