The calyx of Held is perhaps the largest nerve terminal in the mammalian central nervous system. This synapse is involved in auditory processing and plays a key role in sound localization. Synaptogenesis of the calyx occurs quickly. In mice, the processes involved in guiding the axon to the appropriate target cell and the subsequent growth of the terminal are completed in just a few days, before the onset of hearing. This contrasts other commonly studied system of neuronal development that can take 2-3 weeks to properly form connections. Thus, the calyx of Held is an attractive model system to study the processes of synaptogenesis and target selection, because these events occur over a compressed time scale. The goal of this research is to investigate key issues of early neuronal development using the calyx of Held as a model system.
In Aim 1, we will explore the competitive interactions among calyx forming axons that ultimately lead to innervation of postsynaptic neurons by only one calyx of Held terminal. To accomplish this, we will quantify the prevalence of converging calyces onto the same target cells during the initial stages of calyx growth. Establishing the prevalence of convergence and pinpointing when competition occurs in this system will provide a foundation for future studies to investigate the cellular mechanisms involved in competition among inputs.
In Aim 2, we will explore how innervation of calyx of Held affects the development of the postsynaptic neuron. To accomplish this, we will quantify basic, but key, biophysical properties of the postsynaptic neuron during the dynamic period of synaptogenesis. We will also remove the presynaptic inputs to ask whether and when calcyeal innervation is required for the biophysical maturation of the MNTB neurons before the onset of hearing. Together, these results will provide a timeline describing the functional maturation of the calyx of Held and its postsynaptic neuron, and provide insight into how they mature in a coordinated manner. These data will form a foundation for future investigations of the developmental paradigms involved in target selection and synaptogenesis. In the long term, results from these and future studies will translate into useful therapies for repair and regeneration of damaged or diseased nervous tissue. ? ? ?
| Holcomb, Paul S; Hoffpauir, Brian K; Hoyson, Mitchell C et al. (2013) Synaptic inputs compete during rapid formation of the calyx of Held: a new model system for neural development. J Neurosci 33:12954-69 |
| Hoffpauir, Brian K; Kolson, Douglas R; Mathers, Peter H et al. (2010) Maturation of synaptic partners: functional phenotype and synaptic organization tuned in synchrony. J Physiol 588:4365-85 |
| Hoffpauir, Brian K; Marrs, Glen S; Mathers, Peter H et al. (2009) Does the brain connect before the periphery can direct? A comparison of three sensory systems in mice. Brain Res 1277:115-29 |
