017 | Molecular transitions that control functional development during adult neurogenesis

Cellular and Molecular Neurobiology

Author: Melina Couffignal | Email: mcouffignal@leloir.org.ar

Melina Couffignal , Natalí B Rasetto , Alejandro Schinder , Damiana Giacomini

1° Laboratory of Neuronal Plasticity, Leloir Institute – CONICET, Buenos Aires, Argentina

The dentate gyrus (DG) of the hippocampus generates adult-born granule cells (abGCs) throughout life, which are then integrated into pre-established neural circuits, adding plasticity to the network. abGCs require over 8 weeks to reach a mature phenotype and the process can be divided in 4 phases, according to morphological and electrophysiological features. Although developing abGC properties are highly described, the molecular mechanisms underlying the process are still unknown. We proposed that adult neurogenesis is controlled by specific transcriptional regulators and effectors that guide the transitions between stages. To unravel these molecular bases, we studied the transcriptomic profile developing abGCs (see poster by Rasetto et al). Based on a preliminary database containing 2-week-old GCs, we selected effector molecules expressed in immature GCs and evaluated their role during GCs development by functional knock out. We are currently analyzing how different candidate molecules downregulated by CRISPR/Cas9 or shRNAs in vivo affect growth and functional integration of developing abGCs. This approach will allow us to study the role of upstream master genes that regulate adult neurogenesis maturation.