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 GFRα1 in the adult hippocampus, the functional role of this system remains unknown. Here, we show that GDNF, acting through its GFRα1 receptor, controls dendritic structure and spine density of adult-born granule cells, which reveals that GFRα1 is required for their integration into preexisting circuits. Moreover, conditional mutant mice for GFRα1 show deficits in behavioral pattern separation, a task in which adult neurogenesis is known to play a critical role. We also find that running increases GDNF in the dentate gyrus and promotes GFRα1-dependent CREB (cAMP response element-binding protein) activation and dendrite maturation. Together, these findings indicate that GDNF/GFRα1 signaling plays an essential role in the plasticity of adult circuits, controlling the integration of newly generated neurons.
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