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

TRINCHERO, MARIELA F.; SCHINDER, ALEJANDRO F.; BONAFINA, ANTONELA; BEKINSCHTEIN, P; LEDDA, FERNANDA; RIOS, ANTONELLA; PARATCHA, GUSTAVO

Congreso; Gordon Research COnferences in Neurotrophic Factors; 2019

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 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 newly generated neurons.