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Lance Zirpel, Ph.D.
Assistant Professor, Department of Neuroscience
zirpe001@umn.edu
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 Cellular
and molecular mechanisms of neuronal survival and development of calcium
homeostasis.
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. |
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Selected Publications
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Rubel , E.W, T. N. Parks, and L. Zirpel. 2004. Assembling, Connecting and Maintaining the Cochlear Nucleus. Springer Handbook of Auditory Research, Vol 23: Plasticity of the Auditory System , pp 8-48. |
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Sugden, S. G., L. Zirpel, C. J. Dietrich
and T. N. Parks
Development of the specialized AMPA receptors of auditory neurons.
J
Neurobiol 2002; 252:189-202 |
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Lippe, W. R., L. Zirpel, and J. S. Stone
Muscarinic receptors modulate intracellular Ca2+ concentration in
hyaline cells of the chicken basilar papilla.
J
Comp Physiol A Neuroethol Sens Neural Behav Physiol 2002; 188(5):381-395
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Zirpel, L. and T. N. Parks
Zinc inhibition of group I mGluR-Mediated calcium homeostasis in auditory
neurons.
J
Assoc Res Otolaryngol 2001; 2 (2):180-187 |
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Zirpel, L., M. A. Janowiak, C. A. Veltri and T. N. Parks
AMPA receptor-mediated, calcium-dependent CREB phosphorylation in
a subpopulation of auditory neurons surviving activity-deprivation.
J
Neurosci 2000; 20(16):6267-6275 |
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Zirpel, L., M. A. Janowiak, D. A. Taylor and T. N. Parks
Developmental changes in metabotropic glutamate receptor-mediated
calcium homeostasis.
J
Comp Neurol 2000; 421(1):95-106 |
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