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Department of Pharmacology

Department of Pharmacology
 

Ulli Bayer, PhD

Associate Professor


Contact Information:

University of Colorado Denver
Department of Pharmacology
Mail Stop 8303, RC1-North
12800 East 19th Ave
Aurora CO 80045

Phone: (303) 724-3610
Fax: (303) 724-3663
E-mail: ulli.bayer@ucdenver.edu
curriculum vitae

Affiliated Programs

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We are interested in the molecular mechanisms underlying learning, memory and cognition. These higher brain functions are thought to require “synaptic plasticity”, i.e. changes in the strength of the synapses that form the connections between neurons. We are studying the mechanisms by which such changes at individual synapses are initiated and maintained. The main forms of plasticity that we are studying are long-term potentiation (LTP) and long-term depression (LTD) of excitatory synapses in the hippocampus, a brain region required for declarative learning and memory. Additionally, we are interested in how changes at one synapse are communicated to other nearby synapses. For instance, how do excitatory LTD-stimuli also cause long-term potentiation of inhibitory synapses (iLTP) on the dendrites of the same neuron?
Additionally, we apply our fundamental neuroscience findings to a better understanding of neurological disorders. This specifically includes conditions with aberrant synaptic plasticity, such as Down syndrome, schizophrenia, and addiction. However, our recent advances also included neuroprotection after acute injuries such as stroke or global cerebral ischemia. We are particularly excited about the fact that our disease-related projects also lead us to a better understanding of the fundamental mechanisms underlying the brain functions that are impaired in the conditions we study.
Our techniques include sophisticated biochemistry; live-imaging of molecular interactions/movements in heterologous cells and neurons; whole-cell and field electrophysiology; and behavioral studies on mutant mice. The molecules in the focus of our interest are the NMDA-type glutamate receptor (NMDAR) and the Ca2+/calmodulin-dependent protein kinase II (CaMKII). The NMDAR is a Ca2+-conducting channel that is activated by glutamate, the major excitatory neurotransmitter in the mammalian brain; CaMKII is a robust sensor and frequency detector of the NMDAR Ca2+ influx and is unique as its activity can become Ca2+-independent (“autonomous”) after autophosphorylation at T286, a process regarded as molecular memory. The NMDAR and CaMKII have been recognized as central mediators of LTP for over 25 years, but our recent findings demonstrated that CaMKII and its autonomous activity are also required for NMDAR-dependent LTD (Coultrap et al., 2014). Importantly, we found that CaMKII can mediate both of these opposing forms of synaptic plasticity through stimulation-dependent substrate selection (Coultrap et al. 2014; Barcomb et al., 2014). Additionally, CaMKII may mediate the communication of plasticity at excitatory synapses to inhibitory synapses (Marsden et al., 2010), further controlling the excitation/inhibition balance.
Regulation of synaptic strength by CaMKII involves the physical movement of the kinase to and from excitatory and inhibitory synapses. Stimulation-induced CaMKII translocation to excitatory synapses is largely dependent on a regulated direct binding of CaMKII to the NMDAR subunit GluN2B, a binding interaction we have intensively studies over the last 15 years (Bayer et al., 2001; Goodell et al., 2014). We still want to address several important questions and apparent conundrums regarding the GluN2B interaction and translocation to excitatory synapses. For instance, how is input-specificity achieved? I.e. how is translocation to non-stimulated synapses prevented? Additionally, almost nothing is known to date about the mechanisms controlling translocation to inhibitory synapses. Excitingly, we now have a method that allows us to live-monitor the movement of endogenous CaMKII in neurons after different stimulation protocols (using intrabodies specific to CaMKII). In contrast to over-expression of GFP-labelled CaMKII, expressing these intrabodies does not interfere with any type of stimulation-induced CaMKII movement that we have tested so far (by comparing the different live imaging methods to immunostaining).

Current Lab Members

 Results From Personnel : Selected site and subsites
First NameLast NameMiddle InitialDegreePosition
HillaryAllenF.BSGraduate Student
KelseyBarcombM.BAGraduate Student
StevenCoultrapJ.PhDSenior Research Associate
DaytonGoodell BSGraduate Student
VincentZaegel PhDProfessional Research Assistant

 

Previous Trainees

 Results From Personnel : Selected site and subsites
First NameLast NameMiddle InitialDegreePosition
IsabelleBuard PhDPostdoctoral Fellow
StevenCoultrapJ.PhDPostdoctoral Fellow
NicholasHaynes BSProfessional Research Assistant
EricHorneA.PhDPostdoctoral Fellow
HeatherO'LearyE.PhDGraduate Student
RebekahVestS.PhDGraduate Student

 

 

View Dr. Bayer's Publications on PubMed

Selected Publications   

 
Selected Review Articles:
 
Coultrap, S. J., and Bayer, K. U. (2012) Regulation of CaMKII in the processing and storage of synaptic information. Trends in Neuroscience, 35:607-618.
 
Coultrap, S. J., Vest, R. S., Ashpole, N. M., Hudmon, A., and Bayer, K. U. (2011) CaMKII in cerebral ischemia. Acta Pharmacologica Sinica. 32:861-872.
 
 
Selected Research Articles:
 
Coultrap, S. J., Freund, R., O’Leary, H., Sanderson, J., Roche, K., Dell’Acqua, M.L., and Bayer, K. U. (2014) Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection. Cell Reports 6:431-437.
 
Turecek, J., Yuen, G., Han, V. Z., Zeng, X.-H., Bayer, K. U., and Welsh, J. P. (2014) Potentiation of weak electrical coupling by NMDA receptor activation in the mammalian brain. Neuron 81(6):1375-88.
 
Coultrap, S. J., and Bayer, K. U. (2014) Nitric oxide induces Ca2+-independent activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII). J. Biol. Chem. 289:19458-19465.
 
Barcomb, K., Buard, I., Coultrap, S. J., Kulbe, J. R., O’Leary, H., Benke, T.A., and Bayer, K. U. (2014) Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength. FASEB J. 28:3810-3819.
 
Bernard, P. B., Castano, A. M., Bayer, K. U.,and Benke, T.A. (2014) Insights into the Mechanisms of mGluR Mediated Long Term Depression from the Rat Model of Early Life Seizures. Neuropharmacology  84:1-12.
 
Liu, X., Liu, Y., Zhong, P., Wilkinson, B., Bayer, K. U., Qi, J., and Liu, Q. S. (2014) CaMKII activity in the ventral tegmental area gates cocaine-induced synaptic plasticity in the nucleus accumbens. Neuropsychopharmacol. 39:989-999.
 
Loweth, J. A., Li, D., Cortright, J. J., Wilke, G., Jeyifous, O., Neve, R.L., Bayer, K. U., Vezina P. (2013) Persistent reversal of enhanced amphetamine intake by transient CaMKII inhibition. J. Neurosci. 33:1411-1416.
 
Buard, I., Freund, R., Lee, Y.-S., Coultrap, S. J., Dell’Acqua, M. L., Silva, A. J., and Bayer, K. U. (2010) CaMKII "autonomy" is required for initiating but not for maintaining neuronal long-term information storage. J. Neurosci. 30:8214-8220.
 
Marsden, K. C., Semesh, A., Bayer, K. U., and Carroll, R. C. (2010) Selective translocation of CaMKIIa to inhibitory synapses. Proc. Natl. Acad. Sci. 107:20559-20564
 
Vest, R. S., O’Leary, H., Coultrap, S. J., Kindy, M. and Bayer, K. U. (2010) Effective post-insult neuroprotection by a novel CaMKII inhibitor. J. Biol. Chem. 285:20675-20682.
 
Bayer, K. U., LeBel, E., McDonald, G.L., O’Leary, H., Schulman, H. and DeKoninck, P. (2006) Transition from reversible to persistent binding of CaMKII to postsynaptic sites and NR2B. J. Neurosci.. 26:1164-1174.
 
Fink, C., Bayer, K. U., Myers, J. W., Ferrell, J. E. Schulman, H. and Meyer, T. (2003) Selective regulation of neurite extension, movement and branching by the b but not the a isoform of CaMKII. Neuron, 39:283-297.
 
Bayer, K. U., De Koninck, P. and Schulman, H. (2002) Alternative splicing modulates the frequency-dependent response of CaMKII to Ca2+-oscillations. EMBO J., 21:3590-3597.
Positions:
 
We are currently seeking highly motivated individuals for postdoctoral positions. Those with experience in one or more of the following areas are especially encouraged to apply: electrophysiology, cell biology, live cell imaging, and super-resolution imaging. A number of projects incorporate a broad range of techniques, concepts and new tools, offering outstanding training potential. To apply for a postdoc position in the lab, please contact Dr. Bayer directly.
 
Graduate students should arrange rotations through their respective graduate programs. Dr. Bayer is currently a member of the University of Colorado MSTP, BSP, Pharmacology, Neuroscience, and Molecular Biology programs. Out of 20 previous three-months rotations, 9 resulted in authorships on publication from the lab, 2 of them as co-first authors (in J. Biol. Chem., Mol. Biol. Cell, PLoS One, and Brain Res.)
 
 
 
Current Funding:
NIH R01NS081248    (PI: Bayer; 30% effort)           $1,348,611      07/01/2013 – 03/31/2017       
“CaMKII substrate selection in opposing forms of synaptic plasticity” will investigate the functions of newly discovered mechanisms of CaMKII substrate site selection in promotion of LTD versus LTP.
 
NIH R01NS080851 (co-PIs: Bayer/Herson; 25%)     $2,067,267      05/01/2013 – 04/30/2018
“CaMKII in global cerebral ischemia” will utilize our novel CaMKII inhibitor and three CaMKII mutant mouse lines in order to discover mechanisms of neuronal cell death and validate specific therapeutic drug targets.
 
NIH R21DA036300 (PI: Bayer; 10% effort)                         $  383,043       08/01/2013 – 07/31/2016
“Persistent reversal of addiction behavior by a transient treatment” will determine the potential of a novel strategy for addiction therapy.
 
NIH P30 NS048154   (PI: Ribera; 1% effort)            $3,582,245      04/01/2004 – 11/30/2015
“Rocky Mountain Neurological Disorders Core Center”.  Role: Machine shop core director.
 
NIH F31 NS092265   (to Dayton Goodell)               $   90,285        03/01/2015-02/28/2018
 
NIH F31 NS083298    (to Kelsey Barcomb)              $   43,706        12/01/2013-11/30/2015
 
Pending Funding:
Three additional NIH grants (both on basic and on disease mechanisms) are currently pending.