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Role of Cajal-Retzius neurons in the development of neocortical networks in the murine brain

Laufzeit: 01.01.2020 - 31.12.2023

Kurzfassung


Cajal-Retzius neurons (CRNs) represent a transient neuronal population located in the marginal zone of the developing neocortex and in the hippocampus. In the neocortex, they rapidly degenerate by apoptosis during the second postnatal week. CRNs are mostly known for their role in controlling the laminar organization of the neocortex through secretion of the extracellular matrix protein reelin. More recently, experiments in which the density or subtype distribution of CRNs have been modified...Cajal-Retzius neurons (CRNs) represent a transient neuronal population located in the marginal zone of the developing neocortex and in the hippocampus. In the neocortex, they rapidly degenerate by apoptosis during the second postnatal week. CRNs are mostly known for their role in controlling the laminar organization of the neocortex through secretion of the extracellular matrix protein reelin. More recently, experiments in which the density or subtype distribution of CRNs have been modified have demonstrated that CRNs are also required for the establishment of the cell composition and connectivity of postnatal layer 1 and arealization of the developing neocortex. However, the mechanisms that underlie these important functions in early cortical development remain uncertain.

In the current research project, I will investigate whether electrical activity of CRNs plays a role in the maturation of neocortical sensory networks. Experiments will be conducted in the primary somatosensory barrel field (S1BF), a structure that

contains a topographic map of the facial whiskers where each cortical barrel receives inputs from a corresponding whisker. To apprehend which role play CRNs in the maturation of the S1BF, the functional inputs of S1BF CRNs will first be determined using in vivo calcium imaging. The neuronal identity of first-order pre-synaptic partners of S1 CRNs will then be identified using monosynaptic viral retrograde tracing, clearing and immunostaining. Finally, CRNs will be silenced by conditional expression of a Designer Receptor Exclusively Activated by Designer Drugs (DREADD) in CRNs from the Wnt3a lineage. The effect of CRNs silencing on the reelin expression and on the architecture of the S1BF using immunochemistry will be analysed.
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