GDNF and GFRa1 are required for proper integration of adult-born hippocampal neurons

BONAFINA, ANTONELA; TRINCHERO, MARIELA F.; RIOS, AS; BEKINSCHTEIN, P; SCHINDER, ALEJANDRO F.; PARATCHA, G; LEDDA, F

Cell Reports

Cell Press

Lugar: Berlin; Año: 2019

2211-1247

The glial cell line-derived neurotrophic factor, GDNF, is required for the survival and differentiation of diverse neuronal populations during nervous system development. Despite the high expression of GDNF and its receptor GFR 1 in the adult hippocampus, the functional role of this system remains unknown. Here we describe that GDNF, acting through its GFR 1 receptor, controls dendritic structure and spine density of adult-born granule cells, which reveals that GFR 1 is required for their integration into preexisting circuits. Moreover, conditional mutant mice for GFR 1 show deficits in behavioral pattern separation, a task in which adult neurogenesis is known to play a critical role. We also found that running increases GDNF in the dentate gyrus and promotes GFR 1-dependent CREB activation and dendrite maturation. Together, these findings indicate that GDNF/GFR 1 signaling plays an essential role in the plasticity of adult circuits, controlling the integration of newly2generated neurons.