ASTROMAP: EARLY INSIGHTS OF ADULT ASTROGLIOGENESIS IN HEALTH AND DEPRESSION

The adult brain retains a remarkable capacity to generate new cells throughout life, a form of neural plasticity in which both new neurons (neurogenesis) and new astrocytes (astrogliogenesis) arise in cytogenic niches such as the dentate gyrus. While adult-born neurons integrate into existing circuits and support synaptic plasticity, the generation of adult-born astrocytes and their functional impact on networks remain comparatively unexplored. Studies suggest astrogliogenesis is sensitive to internal and external stimuli and is disrupted in several disorders, including stress-induced depression. In line with this, our laboratory has shown that hippocampal adult-born astrocytes (hABA) generation is compromised upon stress. This deficit can be reversed by antidepressant treatment or by transplanting glial-restricted precursor cells, restoring cytogenesis and ameliorating mood-related deficits. Together, these findings suggest that preventing hABA loss, promoting their maturation and integration, or restoring their numbers to physiological levels may counterbalance the glial loss observed in stress-induced depression, and may represent a novel therapy for this disorder. Despite this, the physiological role of hABA and the mechanisms by which they influence depression remain poorly understood. Using Brainbow and Nestin-Cre mouse models, combined with genetic tools to either visualize hABA and label their progeny, or to specifically delete them in a spatiotemporal-dependent manner, imaging, electrophysiological, and transcriptomic approaches, this project aims to functionally characterize hABA and define their sex-dependent role in stress-induced depression. Preliminary extracellular recordings reveal that hABA ablation enhances basal synaptic transmission and alters CA3-CA1 Schaffer collateral long-term potentiation, while the stress protocol produces sex-specific depressive-like phenotypes.