V-083
Loss of GFRα1 in Mice Reveals Behavioral and Neural Signatures of Psychiatric Disorders
Delfina Mercedes Romero1, Maria Muñoz Osorio1, Ana Paula De Vincenti1, Diego Pafundo2, Juan E. Belforte2, Mariano Soiza Reilly3, Fernanda Ledda4, Gustavo Paratcha1
  1. IBCN-UBA-CONICET
  2. IFIBIO-UBA-CONICET
  3. IFIBYNE-UBA-CONICE
  4. IIBBA-FIL-CONICET
Presenting Author:
Delfina Mercedes Romero
delfina.romero@conicet.gov.ar
During the development of the nervous system, the formation of synaptic circuits is tightly regulated through precise control of axonal and dendritic growth. Neurotrophic factors, such as the "glial cell line-derived neurotrophic factor" (GDNF) and its receptor GFRα1, play a pivotal role in dendritic arborization and spine maturation within the cerebral cortex and hippocampus. Disruptions in neuronal connectivity could contribute to the etiology of various neurodevelopmental disorders. Evidence from both human and rodent studies indicates that alterations in the excitatory/inhibitory synaptic balance are a hallmark of neurodevelopmental psychiatric conditions, including schizophrenia, autism spectrum disorder, and Rett syndrome. Furthermore, changes in neural morphology and synaptic architecture may underlie not only synaptic imbalance but also behavioral abnormalities observed in mouse models of these disorders. Despite these findings, the specific role of the GDNF/GFRα1 signaling pathway in the maturation and remodeling of synaptic circuits across distinct forebrain regions remains poorly understood. To address this, we have developed a novel conditional mutant mouse line with targeted ablation of GFRα1 in selected populations of forebrain neurons. This model will enable us to dissect the specific contributions of GDNF/GFRα1 signaling to the development and function of forebrain circuits implicated in neurodevelopmental disorders.