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LOSS OF GFRΑ1 IN MICE REVEALS BEHAVIORAL AND NEURAL SIGNATURES OF NEURODEVELOPMENTAL PSYCHIATRIC DISORDERS
Delfina Romeroand 7 co-authors
Instituto de Biología Celular y Neurociencias, Prof. E. de Robertis. Facultad de Cs. Médicas, Universidad de Buenos Aires. CONICET
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS05-09AM-362
Presentation
Date TBA
Board: PS05-09AM-362
Event Information
Poster Board
PS05-09AM-362
Poster
View posterAbstract
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. Evidence from human and rodent studies indicates that alterations in dendritic arborization and spine morphology, key determinants of synaptic connectivity, are hallmarks of neurodevelopmental psychiatric conditions, including schizophrenia, autism spectrum disorder and Rett syndrome. Despite these findings, the role of the GDNF/GFRα1 signaling pathway in the maturation and remodeling of forebrain synaptic circuits remains poorly understood. To address this, we have developed a novel conditional mutant mouse line with targeted ablation of GFRα1 (cKO) in selected populations of forebrain neurons. The cKO mice showed several alterations in the hippocampal neuronal architecture and physiological activity; accompanied by cognitive behavioral deficits. This model will allow us to dissect the specific contribution of GDNF/GFRα1 signaling to the development and function of forebrain circuits implicated in neurodevelopmental disorders.
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