The immature brain is not a small sized version of the adult brain: its circuits are profoundly different and much less understood. Therefore, studying how neural circuits take shape is essential for several reasons. First, it is important to understand how the normal brain works. Second, it is critical to gain insights into how abnormal brain development contributes to neurological and mental health disorders. Third and last, it is required for a rational approach to create novel therapeutic strategies for diseases that are currently untreatable. Cajal-Retzius cells are transient neurons that play important functions during mammalian corticogenesis, such as control of neuronal migration and cortical lamination. However, their fast network/computational roles, mediated by synaptic transmission, remain rather mysterious and poorly understood. Based on the work that we have already published and on the preliminary data collected during these last three and a half years of funding, we propose to test the overarching hypothesis that Cajal-Retzius cells of the developing hippocampus are an essential component of a microcircuit that is involved, physiologically, in the regulation of synaptic plasticity of specific hippocampal connections, but may also contribute to the well-known vulnerability of this region to seizures. This project has a direct translational relevance because a deeper understanding of cellular mechanisms involved in network functions of the maturing brain is critical to provide insights for novel therapeutic approaches in neurodevelopmental disorders.
This proposal plans to test the broad hypotheses that: (i) Cajal-Retzius cells are critical neuronal elements controlling the plasticity/maturation of an earl hippocampal microcircuit, physiologically associated with spatial memory functions and (ii) may play a role in the well-known vulnerability of young animals to epilepsy. The identification of cel type-specific mechanisms of neuronal development is critical to gain insights into how neural circuits take shape and how abnormal network activity contributes to neurological disorders.
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