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

BELFORTE, JE; PARATCHA, G; OLIVERA, MM; LEDDA, F; ROMERO, DM; SOIZA REILLY, M

Buenos Aires

Congreso; SAN 2022 Meeting; 2022

Sociedad Argentina de Investigación en Neurociencias (SAN)

During nervous system development, the formation of synaptic circuits occurs under a precise control of the axon and dendritic growth. Neuronal abnormal connectivity could contribute to the aetiology of neurodevelopmental disorders. Studies in humans and animal models indicate that alterations on the excitatory/inhibitory synaptic balance are present in neurodevelopmental psychiatric conditions such as schizophrenia, 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 the cerebral cortex and hippocampus. Despite this evidence the role of GDNF/GFRa1 receptor in the maturation and remodelling of synaptic circuits in different forebrain regions still remains poorly understood. To investigate this, we generated new conditional mutant mice with selective ablation of GFRa1 in different populations of forebrain neurons. These mice lines will allow us to determine the specific involvement of GDNF/GFRa1 in forebrain circuits associated with neurodevelopmental disorders.