The sub-ventricular zone (SVZ) of the lateral ventricles is a source of new neurons throughout postnatal development into adulthood. These young neurons migrate through the rostral migratory stream (RMS) to reach the olfactory bulb, where they mature into gamma-aminobutyric acid-producing (GABAergic) interneurons. Recently, experiments from H. Monyer's lab have shown that in addition to the RMS, newly born neurons from the SVZ can also migrate in two other streams termed dorsal migratory stream (DMS) and external migratory stream (EMS), leading to the integration of GABAergic interneurons into other brain areas such as cortex, hippocampus striatum and amygdala. Neuroblasts within these migratory streams are serotonin receptor (5-HT)3A-expressing cells and activation of these receptors is essential for their migration.
So far, little is known about which factors determine migration in the RMS, DMS and EMS. The main goal of this project is to gain insight into the processes of newborn cell migration and maturation in the distinct streams as well as the identification of factors that influence their integration in an already existing microcircuit. We will analyse whether molecules known to be involved in the RMS migration and guidance could also be acting within t he dorsal and external migration streams. In addition, we will analyse the functional significance of postnatal neurogenesis originating in the SVZ at the network level by selective elimination of the 5HT3A expressing cell population.
The project proposed here consists on an integrative research from molecular to behavioural analysis of neuronal migration in the adult mammalian brain. I will take advantage of my formation on molecular and cellular neurobiology but I will also have the possibility of learning other methodologies such as virally mediated gene expression in neurons and time-lapse imaging recording with expert investigators in the field, which represents a great opportunity for my career.
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