Anales RANF

P.56 PARACRINE SIGNALING VIA P2X2/3R IS REQUIRED FOR FUNCTIONAL DEVELOPMENT OF A CENTRAL AUDITORY SYNAPSE Saša Jovanovic 1,2 , Tamara Radulovic 1,3 , Jana Nerlich 1 , Ivan Milenkovic 1,2 1 Carl Ludwig Institute for Physiology, Faculty of Medicine, University of Leipzig, Leipzig, Germany; 2 School of Medicine and Health Sciences, Oldenburg University, Oldenburg, Germany; 3 Carver College of Medicine, University of Iowa, Iowa City, IA, USA. Understanding how early action potential discharges contribute to the maturation of neuronal networks is one of the major challenges in developmental neurophysiology. Following initial development including neuronal differentiation, migration, axon guidance and synaptogenesis, neuronal activity in maturing circuits is guiding the formation of precise sensory maps. In the auditory system, sensory map formation and sharpening depend on the spontaneous activity before hearing onset and extend to the period of early auditory experience. However, it remains elusive how neuronal activity affects different aspects of maturation in the auditory brainstem circuit that is encoding temporal features of sound to compute sound source location. In the developing ventral cochlear nucleus, the first central station along the auditory pathway that receives inputs from the cochlea through the VIII nerve, paracrine ATP signaling enhances firing in a cell-specific and tonotopically-determined manner. Endogenously released ATP activates the P2X2/3R expressed only in bushy cells, and increases the synaptic efficacy of immature synaptic inputs, i.e. endbulbs of Held, by facilitating postsynaptic AP generation and prolonging APs. Developmental down- regulation of P2X2/3R currents occurs simultaneously with an increase in AMPAR currents from high-to-low frequency area. Our in vivo and slice experiments in P2X2/P2X3Dbl-/- mice demonstrate that the P2X2/3R is required for functional maturation of endbulb of Held synapses during the period of early auditory experience.