S-020
Activity-Gated Rescue of Delayed Neuroblast Maturation in the Aging Hippocampus
Natalí Belén Rasetto1, Magali Herrero1, Ariel Berardino2, Damiana Giacomini1, Mariela Trinchero1, Daniela Di Bella3, Paola Arlotta3, Ariel Chernomoretz2, Alejandro Schinder1
  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.
Presenting Author:
Natalí Belén Rasetto
rasettonatali@gmail.com
Adult hippocampal neurogenesis is a conserved, multi-stage process essential for cognitive flexibility and memory. In young animals, adult-born granule cells (aGCs) progress through a well-orchestrated developmental trajectory that lasts for about 10 weeks. Aging significantly reduces the rate and speed of neurogenesis. To uncover the molecular stage-specific effects of aging on the generation of new neurons, we combined permanent lineage tracing of aGCs with single-nucleus RNA sequencing (snRNA-seq) in aged mice. This strategy allowed us to generate a temporally resolved transcriptional atlas of neurogenesis in the aging hippocampus. Our analysis revealed a pronounced accumulation of neurons at a specific postmitotic neuroblast stage. Remarkably, this population was highly responsive to behavioral stimuli: voluntary running reduced neuroblast accumulation to re-engage developing neurons towards later stages along the differentiation trajectory. These findings position postmitotic neuroblasts as critical regulatory nodes in the neurogenic sequence, poised to integrate pro-maturational signals. This work offers a high-resolution framework for dissecting the mechanisms of neurogenic decline and points to potential strategies for rejuvenating hippocampal plasticity in aging.