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Fred Hoerndli

 

 

 

 

 

 

 

  

​Office: W310 Anatomy/Zoology building, Main Campus
Phone: 970-491-7768
Lab Phone: 970-491-6755
Email: frederic.hoerndli@colostate.edu

Fred Hoerndli, PhD

Assistant Professor, Department of Biomedical Sciences
Colorado State University

Education

Second Post-doc: University of Utah
Imaging, genetic and electrophysiological studies which revealed how molecular motors regulated transport of glutamate receptors to synapses in the lab of Dr. Andres V. Maricq using the genetic model C. elegans.

First Post-doc: University of Zurich, Switzerland
Whole genome human SNP mapping in the lab of Dr. Andreas Papassotiropoulos, searching for genetic variations associated with improved episodic memory.

PhD, Neuroscience, University of Zurich, Switzerland
Research on gene network regulation in a cell culture model of Alzheimer's disease, with Dr. Juergen Goetz.

MS, Molecular Biology, University of Lausanne, Switzerland

Research Interests

Information processing by nervous systems depends on the dynamic regulation of synapses. The number of neurotransmitter receptors at synapses is a critical determinant of the strength of synaptic signaling, ultimately impacting learning and memory. Receptors are synthesized in the cell body of neurons and can be differentially delivered to and removed from synapses, some of which can be hundreds of microns away. How do neurons independently regulate neurotransmitter receptor numbers at thousands of synapses? Identifying the molecular and cellular mechanisms required to achieve this level of regulation is fundamental to our understanding of brain function. I am interested in addressing two major questions. How does receptor delivery and maintenance affect synaptic composition? How are these processes differentially regulated during synaptic strengthening or weakening in response to neuronal activity?

Previously, I have undertaken an in vivo analysis of the trafficking of ionotropic glutamate receptors (iGluRs) in the nematode C. elegans. Glutamate is the major excitatory neurotransmitter in most nervous systems and modifying the number of synaptic iGluRs is thought to play a central role in learning and memory. C. elegans is transparent, and has an invariant and well-described nervous system. This allowed me to develop techniques in microscopy to image and quantify real-time trafficking of iGluRs in intact animals. Using these innovative methods, I showed that molecular motors are used to deliver and remove iGluRs to and from synapses thereby regulating synaptic strength.

The ability to measure iGluR transport, and synaptic delivery and removal in an intact, living animal is extremely valuable. The Hoerndli Lab research is organized around these techniques and the following questions: What signaling pathways regulate receptor loading onto motors? How are receptors unloaded from motors at synapses? How is receptor loading and unloading from motors at synapses differentially regulated for plasticity and maintenance? Answering these questions is fundamental to our understanding of how synaptic strength is modified allowing us to learn, remember and modify our behavior.

Model AMPAR transport in a unipolar neuron
Heteromeric and homomeric Glutamate Receptors (GLR-1 and GLR-1/2) are transported by the molecular motor complex Kinesin-1. Neuronal activity, Calcium and CaMKII regulate transport from the cell body as well as delivery and removal at synapses.  The Hoerndli lab research aims to understand how this is achieved and what pathways regulate this process during memory establishment and cellular ageing.


Representative Publications

Hoerndli F.J., A. Kallarackal, and A.V. Maricq (2015) Mobile AMPARs are required for synaptic plasticity. Channels(Austin) 9:230-2. 

Hoerndli F.J., R. Wang, J.E. Mellem, A. Kallarackal, P.J. Brockie, C. Thacker, D.M. Madsen and A.V. Maricq (2015) Neuronal activity and CaMKII regulate kinesin-mediated transport of synaptic AMPARs. Neuron 86: 1-18. (Cited in Faculty 1000) 

Hoerndli F.J.*, D.A. Maxfield*, P.J. Brockie, J.E. Mellem, E. Jensen, R. Wang, D.M. Madsen and A.V. Maricq (2013) Kinesin-1 regulates synaptic strength by mediating the delivery, removal and redistribution of AMPA receptors. Neuron 80:1421-37. Feature article (*, co-first authors) (Cited in Faculty 1000)

Brockie, P.J., M. Jensen, J. Mellem, E. Johnson, R. Wang, D.A. Maxfield, F.J. Hoerndli, D.M. Madsen and A.V. Maricq (2013) Cornichons control ER export of AMPA receptors to regulate synaptic excitability. Neuron 80:129-42. 

Wang, R., J.E. Mellem, M. Jensen, P.J. Brockie, C.S. Walker, F.J. Hoerndli, D.M. Madsen and A.V. Maricq (2012) The SOL-2/Neto auxiliary protein modulates the function of AMPA-subtype ionotropic glutamate receptors. Neuron 75:838-50. 

Jensen, M., F.J. Hoerndli, P.J. Brockie, R. Wang, E. Johnson, D. Maxfield, M.M. Francis, D.M. Madsen and A.V. Maricq (2012) Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system. Cell 149:173-87.

Stetak, A., F. Hörndli, A.V. Maricq, S. van den Heuvel and A. Hajnal (2009) Neuron-specific regulation of associative learning and memory by MAGI-1 in C. elegans. PLoS One 4:e6019.

Hoerndli, F.J., M. Walser, E. Fröhli Hoier, D. de Quervain, A. Papassotiropoulos and A. Hajnal (2009) A conserved function of C. elegans CASY-1 calsyntenin in associative learning. PLoS One 4:e4880.

Hoerndli, F.J., S. Pelech, A. Papassotiropoulos and J. Götz (2007) Abeta treatment and P301L tau expression in an Alzheimer’s disease tissue culture model act synergistically to promote aberrant cell cycle re-entry. Eur J Neurosci 26:60-72.

Huentelman, M.J., A. Papassotiropoulos, D.W. Craig, F.J. Hoerndli, J.V. Pearson, K.D. Huynh, J. Corneveaux, J. Hänggi, C.R. Modardori, A. Buchmann, E.M. Reiman, K. Henke, D.J. de Quervain and D.A. Stephan (2007) Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance. Mol Genet 16:1469-77.

Papassotiropoulos, A., D.A. Stephan, M.J. Huentelman, F.J. Hoerndli, D.W. Craig, J.V. Pearson, K.D. Huynh, F. Brunner, J. Corneveaux, D. Osborne, M.A. Wollmer, A. Aerni, D. Coluccia, J. Hänggi, C.R. Mondadori, A. Buchmann, E.M. Reiman, R.J. Caselli, K. Henke and D.J. de Quervain (2006) Common Kibra alleles are associated with human memory performance. Science 314:475-78.

Hoerndli, F.J., M. Toigo, A. Schild and J. Götz (2004) Reference genes identified in SH-SY5Y cells using custom-made gene arrays with validation by quantitative polymerase chain reaction. Anal Biochem 335:30-41.

Chen, F., M.A. Wollmer, F. Hoerndli, G. Münch, B. Kuhla, E.I. Rogaev, M. Tsolaki, A. Papassotiropoulos and J. Götz (2004) Role for glyoxalase I in Alzheimer’s disease. Proc Natl Acad Sci USA 101:7687-92.

Ferrari, A., F. Hoerndli, T. Baechi, R.M. Nitsch and J Götz (2003) beta-Amyloid induces paired helical filament-like tau filaments in tissue culture. J Biol Chem 278:40162-68.

Streffer, J.R., A. Papassotiropoulos, P. Kurosinski, A. Signorell, M.A. Wollmer, M. Tsolaki, V. Iakovidou, F. Hörndli, J. Bosset, J. Götz, R.M. Nitsch and C. Hock (2003) Saitohin gene is not associated with Alzheimer's disease. J Neurol Neurosurg Psychiatry 74:362-63.

Reviews

Götz, J., D. David, F. Hoerndli, Y.D. Ke, N. Schonrock, A. Wiesner, T. Fath, L. Bokhari, Y.A. Lim, N. Deters and L.M. Ittner (2008) Functional genomics dissects pathomechanisms in tauopathies: mitosis failure and unfolded protein response. Neurodegener Dis 179-81.

Hoerndli, F., D.C. David and J. Götz (2005) Functional genomics meets neurodegenerative disorders. Part II: Application and data integration. Prog Neurobiol 76:169-88.

David, D.C., F. Hoerndli and J. Götz (2005) Functional genomics meets neurodegenerative disorders. Part I: Transcriptomic and proteomic technology. Prog Neurobiol 76:153-68.

Götz, J., J.R. Streffer, D. David, A. Schild, F. Hoerndli, L. Pennanen, P. Kurosinski and F. Chen (2004) Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy. Mol Psychiatry 9:664-83.

Götz, J., A. Schild, F. Hoerndli and L. Pennanen (2004) Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight from transgenic mouse and tissue-culture models. Int J Dev Neurosci 22:453-65.