CONICET | Buscador de Institutos y Recursos Humanos

Hippocampal neuronal network is composed by excitatory and inhibitory synapses from glutamatergic and GABAergic neurons respectively. Synapse formation is thought to be regulated in a bidirectional fashion between pre and postsynaptic membranes. It?s known that several types of cell adhesion molecules play an important role in this process. Incorrect synaptic connections has been shown to lead to several neurological diseases, therefore the identification of new molecules that regulate synapse formation is an important step to understand the mechanisms underlying these processes. Glial cell line-derived neurotrophic factor (GDNF) signaling require two types of receptors: the GPI-anchored receptor GFRα1, specialized in ligand binding, and a transmembrane receptor that could be the receptor tyrosine kinase RET or neural cell adhesion molecule (NCAM). In the hippocampus GFRα1 is present in pre and postsynaptic membranes and it is able to interact in trans when it binds GDNF. Furthermore, it is expressed in high levels during the main period of rodent hippocampal synaptogenesis. Nonetheless, the role of GFRα1 in the postsynaptic membrane and synaptic maturation remains still unknown. The lethality of the GFRα1 knock-out mice before birth has hindered the analysis of the main function of this receptor in the postnatal hippocampus. The aim of this study was to determinate the role of GFRα1 during hippocampal synaptogenesis and plasticity. In order to study if this receptor is required for the appropriate integration of glutamatergic neurons in the normal hippocampus development and the physiological relevance of this receptor in hippocampal connectivity, we are analyzing a GFRα1 conditional mice. Our preliminary results suggest that GFRα1 could be involved in hippocampal postsynaptic maturation and neuronal plasticity.