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Wiring up visual circuits: Interplay between gene expression and spontaneous and experience-dependent activity


A fundamental feature of the developing neural circuits is their ability to change in response to sensorial experience. This phenomenon has been particularly observed during the generation of cortical maps, where altering the pattern of sensory experience changes the spatial organization of sensory representations. The mechanisms underlying this form of plasticity include synaptic modification such as long-term potentiation and long-term depression, classically referred to as Hebbian-based rules. Today, there is growing evidence that prior to sensory experience, neural electrical activity plays a role in early brain development. In several developing circuits including retina, spinal cord, hippocampus and cortex, there are transient events that cause these circuits to spontaneously generate waves of correlated activity. However, the cellular and molecular mechanisms that translate these spontaneous activity patterns into mature neural circuits that will eventually be ruled by Hebbian-type plasticity remain largely unknown. The first part of this proposal deals with early events in development in which sensory-independent factors outline a first draft of neuronal connections: How spontaneous activity and molecular factors integrate to shape initial neuronal connectivity? Based in our own findings and using the mammalian visual system as a model, we will genetically silence spontaneous activity in a specific population of neurons and will screen for molecules induced by spontaneous waves. We will also dissect the relative contribution of the different stages of spontaneous waves and will try to understand the relationship of spontaneous activity with different families of axon guidance molecules during the assembly of neural circuits. In the second part of the project we will determine to what extent cortical maps wiring depends on the formation of early thalamic properties and how this wiring may be modified by experience to optimally support information processing.

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