Ivan Milenkovic: Activity-dependent development of precise temporal coding at calyceal synapses

Understanding how early action potential discharges contribute to the development of neuronal networks is one of the major challenges in developmental neurophysiology. Following initial developmental processes, the patterned, sensory-independent activity in maturing neuronal circuits is believed to guide the formation of precise sensory maps. We hypothesize that not just the activity, but the pattern of prehearing activity, determines the development of synaptic transmission at giant calyceal synapses in the auditory brainstem. We assess the role of activity pattern in maturation of the endbulb- and calyx of Held-synapses in a mice model with Poisson-like firing before hearing onset (P2X2/P2X3Dbl-/-). The contribution of early auditory experience is investigated in a mouse model with conditional cell-specific hair cell ablation at different developmental stages (Pou4f3DTR/+). Experiments are designed for complementary use of in vivo- and slice-electrophysiology to assess functional processing through systemic acoustic stimulation and reveal underlying cellular mechanisms.