Schizophrenia spectrum disorders have been linked to developmental alterations in the migration, maturation and function of projection neurons in brain regions such as the human dorsolateral prefrontal cortex. To explain these defects, many candidate risk genes have been proposed, some of which belonging to the 22q11.2DS region. This is the case of DGCR2, a schizophrenia risk gene previously shown in the lab to control the migration of superficial layer neocortical projection neurons.

For this thesis, we focused on the implication of Dgcr2 in the post-natal maturation of projection neurons dendritic spines. In this purpose, we performed a morphological analysis of spines coming from mice brains which underwent knock-down of Dgcr2 expression specifically in projection neurons during their development. We noticed a globally more immature dendritic spine profile in the Dgcr2 knock-down condition, a result compatible with previous findings in schizophrenia.

As a second aim, we also analysed results from a new genetic transfection method: in utero electroporation using a triple-electrode probe. We tested if this approach allows us to target efficiently, selectively and bilaterally a murine brain region called medial prefrontal cortex. This latter is known for its strong anatomical and functional homologies with the human dorsolateral prefrontal cortex. We showed that this technique presents a lot of advantages in comparison with its previous version using two electrodes, but also some limitations. We also identified some parameters in the procedure we have to improve in order to create a valid murine behavioural model of a medial prefrontal Dgcr2 knock-down alteration.