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

TRINCHERO, MARIELA F.; BEKINSCHTEIN, P; LEDDA, F; BONAFINA, A; DE VINCENTI, PAULA; PARATCHA, G; RIOS, AS; SCHINDER, ALEJANDRO F.

New Port, Rhode Isalnd

Conferencia; Gordon Research Conference-Neurotrophic Mechanisms in Health and Disease; 2019

Gordon Research Conferences

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 GFRa1 in the adult hippocampus, the functional role of this system remains unknown. Here we describe that GDNF, acting through its GFRa1 receptor, controls dendritic structure and spine density of adult-born granule cells, which reveals that GFRa1 is required for their integration into preexisting circuits. Moreover, conditional mutant mice for GFRa1 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 GFRa1-dependent dendrite maturation. Together, these findings indicate that GDNF/GFRa1 signaling plays an essential role in the plasticity of adult circuits, controlling the integration of newly generated neurons.