Cellular and Molecular Neurobiology
Author: Natali Belen Rasetto | email: rasettonatali@gmail.com
Natalí B. Rasetto 1°, Damiana Giacomini 1°, Ariel Berardino 2°, Tomás Vega Waichman 2°, M. Luz Vercesi 2°, Daniela Di Bella 3°, Juliana Brown 3°, Chiara Gerhardinger 3°, Sara Sime 3°, Paola Arlotta 3°, Ariel Chernomoretz 2° and Alejandro Schinder 1°
1° Laboratory of Neuronal Plasticity, Leloir Institute-CONICET, Buenos Aires, Argentina.
2° Laboratory of Integrative Systems Biology, Leloir Institute-CONICET, Buenos Aires, Argentina
3° Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
Adult hippocampal neurogenesis plays a critical role in spatial memory formation and retrieval, context discrimination, and clearance of memory traces. In the mouse dentate gyrus, the maturation of adult-born granule cells (GCs) lasts several weeks and can be divided in 4 phases based on electrophysiological and morphological features. Behavioral stimuli such as spatial learning and physical exercise can modulate the duration of these stages. However, the molecular mechanisms underlying neuronal maturation remain unknown. We propose that such progression is driven by sequential changes in gene expression programs that might be revealed by transcriptomic analysis. Clusterization of two separate datasets obtained by single nuclei RNAseq experiments identified multiple partitions that define a pathway from radial glia-like cells to a mature neuronal phenotype. Several clusters represent intermediate stages of maturation that were previously unknown. Among them, we identified a cluster of immature GCs resembling a state of high activity, as well as mature GCs that reveal transcriptional differences revealing their dorso-ventral location within the hippocampus. Finally, the emergence of novel transcriptional markers for the intermediate states was validated by in situ hybridization using RNAscope. This analysis allowed to reconstruct the signatures involved in adult neuronal development and function with high temporal resolution.