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Faculty Detail    
Name LYNN DOBRUNZ
 
Campus Address SHEL 902 Zip 2182
Phone  205-934-7923
E-mail  dobrunz@uab.edu
Other websites Department Site
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Neurobiology  Neurobiology Associate Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Associate Professor
Center  Civitan International Research Center  Civitan International Research Center Associate Professor
Center  Comprehensive Ctr for Healthy Aging  Comprehensive Ctr for Healthy Aging Associate Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Associate Professor
Center  Ctr for Glial Bio in Med  Ctr for Glial Bio in Med Associate Professor

Graduate Biomedical Sciences Affiliations
Cellular and Molecular Biology Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Neuroscience 
Neuroscience Graduate Program 
Neurosciences 

Biographical Sketch 
Lynn E. Dobrunz received her S.B. in Engineering and Applied Sciences from Harvard University in 1988. She was awarded a Ph.D. in Biomedical Engineering from The Johns Hopkins University School of Medicine in 1994. She did postdoctoral work with Charles F. Stevens in the Department of Molecular Neurobiology at The Salk Institute in La Jolla, CA, and joined the faculty of UAB in 1999. She is currently an Associate Professor of Neurobiology and an Associate Director of the UAB Comprehensive Neuroscience Center.

Society Memberships
Organization Name Position Held Org Link
Society for Neuroscience     

Research/Clinical Interest
Title
Synaptic Transmission and Plasticity in Hippocampus
Description
My labís research focuses on understanding the role of inhibitory interneurons in regulating synaptic plasticity and circuit function in hippocampus, both in normal brain and in rodent models of neuropsychiatric disorders. We currently have three major areas of investigation. First, we are investigating the role of short-term plasticity in regulating the balance between excitation and inhibition in hippocampus. Alteration in the E/I balance is emerging as a general principle underlying a wide variety of disorders, including schizophrenia, bipolar disorder, depression, autism, Down Syndrome, and epilepsy. Short-term synaptic plasticity dynamically regulates both excitatory and inhibitory synapses, causing their strength to be rapidly modified depending on the pattern of input activity. However, relatively little is known about the overall effects of short-term plasticity on the E/I balance, and how this affects circuit function. We are investigating this in hippocampus, using a combination of electrophysiology and voltage-sensitive dye imaging in hippocampal brain slices. In a second (related) project, we are investigating the effects of interneuron transcriptional dysregulation on hippocampal circuit function. Transcriptional dysregulation in inhibitory interneurons occurs in a variety of disorders, including schizophrenia, bipolar disorder, and epilepsy. In particular, a decrease in the calcium binding protein parvalbumin, which is found in an important subtype of GABAergic interneurons, is one of the most prevalent findings in postmortem tissue from schizophrenia patients. PGC-1α (peroxisome proliferator activated receptor  coactivator 1α) is a transcriptional co-activator in interneurons that regulates transcription of parvalbumin. Genetic deletion of PGC-1α in mice results in decreased protein expression of parvalbumin in interneurons, as well as decreases in several other synaptic proteins that have been shown to be reduced in postmortem tissue from schizophrenia patients. We are using PGC-1α-/- mice as a way to investigate the multi-factorial effects of interneuron transcriptional dysregulation on hippocampal synaptic and circuit function, using a combination of approaches including electrophysiology, voltage-sensitive dye imaging, optogenetics, pharmacology, and behavior. We are currently determining the effects transcriptional dysregulation on the dynamics of the E/I balance, on the regulation of hippocampal circuit function by dopamine, and on hippocampal dependent behavior. In a third project, we are investigating the effects of Neuropeptide Y (NPY) on hippocampal circuit function and behavior. NPY is an endogenous neuropeptide with robust anxiolytic (anti-anxiety) properties that has been implicated in a wide variety of anxiety disorders, including posttraumatic stress disorder (PTSD). It is released by a subset of inhibitory interneurons that also release GABA. We are studying the mechanisms that regulate the firing of NPY interneurons in hippocampus, the release of NPY, and the effects of NPY on the E/I ratio and on hippocampal circuit function. We are also investigating the role of alterations in NPY release in a rodent model of stress-induced anxiety/PTSD, and testing the effects of manipulating NPY levels on anxiety and the susceptibility to PTSD-like symptoms.

Selected Publications 
Publication PUBMEDID
Dougherty, S. E., A. F. Bartley, E. K. Lucas, J. J. Hablitz, L. E. Dobrunz and R. M. Cowell (2014). "Mice lacking the transcriptional coactivator PGC-1alpha exhibit alterations in inhibitory synaptic transmission in the motor cortex." Neuroscience 271: 137-48.
 
24769433 
Walters, B. J., J. J. Hallengren, C. S. Theile, H. L. Ploegh, S. M. Wilson and L. E. Dobrunz (2014). "A catalytic independent function of the deubiquitinating enzyme USP14 regulates hippocampal synaptic short-term plasticity and vesicle number." J Physiol 592(Pt 4): 571-86.
 
24218545 
Marshall, A. G., J. A. Watson, J. J. Hallengren, B. J. Walters, L. E. Dobrunz, L. Francillon, J. A. Wilson, S. E. Phillips and S. M. Wilson (2013). "Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14)." PLoS One 8(12): e84042.
 
24358326 
Jin, Y. N., P. C. Chen, J. A. Watson, B. J. Walters, S. E. Phillips, K. Green, R. Schmidt, J. A. Wilson, G. V. Johnson, E. D. Roberson, L. E. Dobrunz and S. M. Wilson (2012). "Usp14 deficiency increases tau phosphorylation without altering tau degradation or causing tau-dependent deficits." PLoS One 7(10): e47884.
 
23144711 
Sun, H.Y., A.F. Bartley, and L.E. Dobrunz. (2009). Calcium-permeable presynaptic kainate receptors involved in excitatory short-term facilitation onto somatostatin interneurons during natural stimulus patterns. J Neurophysiol 101(2):1043-1055.  19073817 
Speed, H.E. & L.E. Dobrunz (2009). Developmental changes in short-term facilitation are opposite at temporoammonic synapses compared to Schaffer collateral synapses onto CA1 pyramidal cells. Hippocampus 19(2): 184-204.   18777561 
Walters, B.J. , Campbell, S.L., P.C. Chen, L.E. Dobrunz, J.A. Wilson, K. Artavanis-Tsakonas, H.L. Ploegh, A.P. Taylor, D.G. Schroeder, G.A. Cox, & S.M. Wilson (2008). "Differential effects of Usp14 and Uch-L1 on the ubiquitin-proteasome system and synaptic activity." Molecular and Cellular Neuroscience 39(4):539-548.   18771733 
Scheiderer, C.L., M.E. McCutcheon, L.E. Dobrunz, & L.L. McMahon (2008). "Coactivation of M1 muscarinic and alpha1 adrenergic receptors stimulates ERK and induces long-term depression at CA3-CA1 synapses in rat hippocampus." J. Neurosci 28:5350-5358.   18480291 
Speed, H.E. & L.E. Dobrunz (2008). "Developmental decrease in short-term facilitation at Schaffer collateral synapses in hippocampus is mGluR1 sensitive." J. Neurophysiol 99:799-813.   18032567 
Crimmins, S., Y. Jin, C. Wheeler, A. K. Huffman, C. Chapman, L. E. Dobrunz, A. Levey, K. A. Roth, J. A. Wilson & S. M. Wilson (2006). "Transgenic rescue of ataxia mice with neuronal-specific expression of ubiquitin-specific protease 14." J Neurosci 26(44): 11423-31.   17079671 
Sun, H. Y. & L. E. Dobrunz (2006). "Presynaptic kainate receptor activation is a novel mechanism for target cell-specific short-term facilitation at Schaffer collateral synapses." J Neurosci 26(42): 10796-807.  17050718 
McCutchen, E., C. L. Scheiderer, L. E. Dobrunz & L. L. McMahon (2006). "Coexistence of muscarinic long-term depression with electrically induced long-term potentiation and depression at CA3-CA1 synapses." J Neurophysiol 96(6): 3114-21.   17005622 
Scheiderer, C. L., E. McCutchen, E. E. Thacker, K. Kolasa, M. K. Ward, D. Parsons, L. E. Harrell, L. E. Dobrunz & L. L. McMahon (2006). "Sympathetic sprouting drives hippocampal cholinergic reinnervation that prevents loss of a muscarinic receptor-dependent long-term depression at CA3-CA1 synapses." J Neurosci 26(14): 3745-56.  16597728 
Dekay, J. G., T. C. Chang, N. Mills, H. E. Speed & L. E. Dobrunz (2006). "Responses of excitatory hippocampal synapses to natural stimulus patterns reveal a decrease in short-term facilitation and increase in short-term depression during postnatal development." Hippocampus 16(1): 66-79.   16261553 
Sun, H. Y., S. A. Lyons & L. E. Dobrunz (2005). "Mechanisms of target-cell specific short-term plasticity at Schaffer collateral synapses onto interneurones versus pyramidal cells in juvenile rats." J Physiol 568(Pt 3): 815-40.   16109728 
Scheiderer, C. L., L. E. Dobrunz & L. L. McMahon (2004). "Novel form of long-term synaptic depression in rat hippocampus induced by activation of alpha 1 adrenergic receptors." J Neurophysiol 91(2): 1071-7.   14573563 
Dobrunz, L. E. (2002). "Release probability is regulated by the size of the readily releasable vesicle pool at excitatory synapses in hippocampus." Int J Dev Neurosci 20(3-5): 225-36.   12175858 
Dobrunz, L. E. and C. C. Garner (2002). "Priming plasticity." Nature 415(6869): 277-8.  11796993 
Dobrunz, L. E. and C. F. Stevens (1999). "Response of hippocampal synapses to natural stimulation patterns." Neuron 22(1): 157-66.   10027298 
Dobrunz, L. E. (1998). "Long-term potentiation and the computational synapse." Proc Natl Acad Sci U S A 95(8): 4086-8.   9539692 
Dobrunz, L. E., E. P. Huang and C.F. Stevens. (1997). "Very short-term plasticity in hippocampal synapses." Proc Natl Acad Sci U S A 94(26): 14843-7.  9405701 
Zador, A. M. and L. E. Dobrunz (1997). "Dynamic synapses in the cortex." Neuron 19(1): 1-4.   9247258 
Dobrunz, L. E. and C. F. Stevens (1997). "Heterogeneity of release probability, facilitation, and depletion at central synapses." Neuron 18(6): 995-1008.  9208866 
Dobrunz, L. E., P. H. Backx, et al. (1995). "Steady-state [Ca2+]i-force relationship in intact twitching cardiac muscle: direct evidence for modulation by isoproterenol and EMD 53998." Biophys J 69(1): 189-201.   7669896 
Dobrunz, L. E. and M. R. Berman (1994). "Effect of temperature on Ca(2+)-dependent and mechanical modulators of relaxation in mammalian myocardium." J Mol Cell Cardiol 26(2): 243-50.   8006985 
Dobrunz, L. E., D. G. Pelletier, et al. (1990). "Muscle stiffness measured under conditions simulating natural sound production." Biophys J 58(2): 557-65.   2207252 

Keywords
anxiety, schizophrenia, hippocampus