GDNF acting through GFRa1 mediates the integration of new neurons into preexisting hippocampal circuits

TRINCHERO, MARIELA F.; SCHINDER, ALEJANDRO F.; BONAFINA, A; MACARIA, D; LEDDA, F; RIOS, AS; PARATCHA, G

CABA

Congreso; Xth Meeting of the Latin American Society for Developmental Biology (LASDB); 2019

LASDB

The dentate gyrus (DG) of the mammalian hippocampus continuously generates new neurons during adulthood. Newborn granule cells (GCs) become functionally active and contribute to learning and memory, especially during their maturation phase. The transition of proliferative progenitor cells to fully differentiated neurons is controlled by an intrinsic cellular program, as well as extrinsic environmental cues, such as neurotrophic factors. We studied the role of glial cell line-derived neurotrophic (GDNF) and its receptor, GFRα1, in adult neurogenesis by deleting GFRα1 in adult progenitor cells. Our results revealed that adult born GCs derived from mice deficient in GFRα1 showed reduced dendritic complexity and a decrease in spine density compared with control mice neurons, revealing that GFRα1 is required for their proper integration into preexisting circuits. The ablation of GFRα1 in adult hippocampal progenitors was associated with behavioral deficits in a pattern separation behavioral test, a task in which adult neurogenesis is known to play a critical role. GFRα1 conditional mice were incapable of performing the test exhibiting failures in spatial memory processing. We also found that running increases GDNF in the DG and promotes GFRα1-dependent dendrite maturation. Overall, this data suggests that GDNF/GFRα1 plays an essential role in role in adult hippocampal neurogenesis.