Christopher von Bartheld, M.D.

Professor

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We are interested in the function of neurotrophic factors in the developing central nervous system. Neurotrophic factors are messengers in the communication between neurons. They regulate neuronal differentiation and may he instrumental in the formation, stabilization and plasticity of synapses. Targeting of neurotrophic factors to their proper intracellular destination is essential for trophic signalling. Our goal is to understand how trophic factors regulate the development and connectivity of neural circuits. A major focus of our lab is to determine how neurotrophic factors are transported along the axon and how they are released from the axon terminals. We use several model systems, including the developing visual system of chick embryos and rodents as well as the hypoglossal motor nucleus to quantify anterograde and retrograde axonal transport of the neurotrophic factors (Fig. 1).

Fig 1. Transport of radio-iodinated NT-3 from the retina to the isthmo-optic nucleus (ION) and the optic tectum (TeO)) in chick embryos. (von Bartheld, et al., Neuron 12:639-654, 1994 and Nature 379:830-833. 1996)

We manipulate with pharmacological agents the release of these factors from nerve terminals, and we localize them by immunohistochemical and autoradiography techniques at both the light- and electron microscopic level (Fig. 2). By combining molecular, morphological, and pharmacological techniques, we hope to gain insights into the mechanisms and dynamics of trafficking of neurotrophic factors and to better understand how they affect the development, plasticity and possibly regeneration of neuronal connections in the brain.

Fig. 2. Accumulation of NT-3 in terminals of the optic nerve after anterograde axonal transport (von Bartheld et al., Nature 379:830-833,1996).

A second major focus of my lab is the function of neurotrophic factors in the developing oculomotor system, with the long-term goal to strengthen weak eye muscles and their innervation. A third topic of interest is the improvement of methods for counting particles in microscopic tissue sections (part of UNR's COBRE, PI: J. Hume). Workers in the lab include Rafal Butowt, Ph.D. (Res. Assistant Professor: axonal transport of trophic factos and pathogens, electron microscopy and molecular biology), Larisa Baryshnikova (postdoctoral fellow: electron microscopy and quantitative morphology), two graduate students: Scott Croes (neuromuscular development, immunocytochemistry, fluorescence imaging, and electrophysiology/ force measurements), and Chengyuan Feng (Transport of trophic factors, RT-PCR, molecular biology) and one medical student. We are also interested in the evolution of neurotrophic factors and recently organized an international symposium on this topic (“Karger workshop” of the J.B. Johnston Club, a satellite event at the Annual Meeting of the Society for Neuroscience, Nov. 10, Washington DC, 2005), published as a special issue in Brain, Behavior & Evolution, 2006.

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Selected Publications