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Lance Zirpel, Ph.D. Assistant Professor, Department of Neuroscience E-mail: zirpe001@umn.edu

Research Interests:

My research program has two main foci. The first is aimed at investigating the cellular and molecular mechanisms of central auditory neuron survival following activity deprivation. In the absence of afferent activity, a subpopulation of cochlear nucleus neurons in embryonic and early post-hatch chicks, as well as juvenile mice, die, while the remainder undergo profound changes in morphology, metabolism and physiology. Phosphorylation and activation of the transcription factor CREB are required for neuronal survival following activity deprivation in both models. What signaling pathways lead to CREB phosphorylation and activation? What are the mechanisms of this activation? Why does it occur only in a subpopulation of activity-deprived neurons? What are the consequences of CREB activation? What genes are transcribed that allow the neurons to survive? These questions are addressed using transfection of auditory neurons with in ovo microelectroporation, immunohistochemistry, Western blotting, and dynamic fluorescent imaging.

The second focus of my research program is investigating the development of neuronal calcium homeostasis mechanisms. Cochlear nucleus neurons receive high frequency, glutamatergic synaptic input from the eighth cranial nerve. Consequently, mechanisms must be in place to prevent excitotoxic hypercalcemia. Auditory neurons in the chick depend upon metabotropic glutamate receptor-mediated mechanisms of calcium homeostasis to maintain physiologic levels of intracellular calcium. How do these mechanisms develop? What role does synaptic activity play in the development and implementation of these mechanisms? These questions are addressed using the same techniques listed above along with electrophysiology and dynamic calcium imaging.

Most Cited Publications:

Rubel, E.W, T. N. Parks, and L. Zirpel. 2004. Assembling, Connecting and Maintaining the Cochlear Nucleus. Springer Handbook of Auditory Research: Development of the Auditory System. In press.

Lippe, W. R., L. Zirpel, and J. S. Stone. 2002. Muscarinic Receptors Modulate Intracellular Ca2+ Concentration in Hyaline Cells of the Chicken Basilar Papilla. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 188(5): 381-395.

Sugden, S. G., L. Zirpel, C. J. Dietrich and T. N. Parks. 2002. Development of the Specialized AMPA Receptors of Auditory Neurons. J Neurobiol 52:189-202

Zirpel, L. and T. N. Parks. 2001. Zinc Inhibition of Group I mGluR-Mediated Calcium Homeostasis in Auditory Neurons. J Assoc Res Otolaryngol, 2 (2): 180-187.

Zirpel, L., M. A. Janowiak, D. A. Taylor and T. N. Parks. 2000. Developmental Changes in Metabotropic Glutamate Receptor-Mediated Calcium Homeostasis. J Comp Neurol 421(1): 95-106.

Zirpel, L., M. A. Janowiak, C. A. Veltri and T. N. Parks. 2000. AMPA Receptor-Mediated, Calcium-Dependent CREB Phosphorylation in a Subpopulation of Auditory Neurons Surviving Activity-Deprivation. J Neurosci 20 (16): 6267-6275.

Current Graduate Students:

Bridget Campion (Neuroscience, University of Minnesota).

Jessie Luoma (Neuroscience, University of Minnesota).