Role of GDNF/GFRa1 receptor in circuits associated with neurodevelopmental disorders

ROMERO, D.M; DE VINCENTI, A.P; MUÑOZ OSORIO, M; BELFORTE, J.E; SOIZA-REILLY, M; LEDDA, M.F; PARATCHA, G

Simposio; Frontiers in Biosciences 4 Symposium; 2023

Max Planck Institute- IBIOBA

During nervous system development, the formation of synaptic circuits occurs undera precise control of the axon and dendritic growth. Neuronal abnormal connectivitycould contribute to the aetiology of neurodevelopmental disorders. Studies inhumans and animal models indicate that alterations on the excitatory/inhibitorysynaptic balance are present in neurodevelopmental psychiatric conditions such asschizophrenia, autism spectrum disorders and Rett syndrome. Neurotrophic factors,like the glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRalpha1(GFRa1) play a critical role in dendritic arborisation and spine maturation in thecerebral cortex and hippocampus. Despite this evidence, the role of GDNF/GFRa1receptor in the maturation and remodelling of synaptic circuits in different forebrainregions still remains poorly understood. To investigate this, we generated newconditional mutant mice with selective ablation of GFRa1 in different populations offorebrain neurons. These mice lines will allow us to determine the specificinvolvement of GDNF/GFRa1 in forebrain circuits associated withneurodevelopmental disorders.