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Faculty Detail Faculty Entry   
Name LORI L MCMAHON WAKEFIELD  
Campus Address MCLM 964 Zip 0005
Phone 205-934-3523
E-mail mcmahon@uab.edu" id="FacultyDetail1EmailAddress"><a href="mailto:mcmahon@uab.edu">mcmahon@uab.edu</a>
URL http://www.physiology.uab.edu/McMahon.htm
 
 

Department Affiliations(s)
Appointment Type Department Division Rank
Center  Neurology   Alzheimer's Disease Center Professor
Center  Center for Aging  Center for Aging Professor
Center  Civitan International Research Center  Civitan International Research Center Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Professor
Center  Cell, Developmntl, & Integrative Biology  Ctr for Exercise Medicine Professor
Center  Medicine  Med - Cardiovascular Disease Professor
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Secondary  Neurobiology  Neurobiology Assistant Professor

Biographical Sketch 
Dr. Lori McMahon,Professor, received her B.A. in Biology/Chemistry from Southern Illinois University in Edwardsville and her Ph.D. from St. Louis University Health Sciences Center in St. Louis, Missouri. Dr. McMahon did Postdoctoral Training at Duke University Medical Center and, in 1998, joined the faculty of UAB.

Society Memberships
Organization Name Position Held Org Link
Society for Neuroscience     
 

Research/Clinical Interest
Title
Synaptic plasticity and hippocampal dependent learning
Description
My laboratory has three major areas of investigation:
First, we are investigating the mechanisms by which muscarinic and adrenergic receptors modulate synaptic function and plasticity in hippocampus and visual cortex. Specifically, we are examining the molecular mechanisms that underlie a form of long-term depression (LTD) at glutamate synapses that is induced by activation of M1 muscarinic or alpha1 adrenergic receptors and how this synaptic mechanism interacts with other well-characterized forms of long-term plasticity. In addition, we are pursuing the consequences of lesion of the cholinergic and adrenergic inputs to hippocampus and visual cortex on the ability of synapses to express plasticity. Degeneration of cholinergic and adrenergic innervation that occurs in neurodegenerative diseases and aging is known to cause cognitive deficits, thus determining how synaptic function is altered following loss of these inputs could have significant clinical benefit. These studies employ electrophysiology in brain slices and cellular techniques including immunohistochemistry and western blot analysis.

In a second project, we are pursuing the effects of estradiol on hippocampal synapse density and synaptic transmission and plasticity. Elevated circulating levels of estradiol enhance memory performance and alterations in hippocampal function are likely to be causally related. We are particularly interested in determining how loss of estradiol during aging impacts hippocampal function and whether hormone replacement therapy can activate estradiol-dependent mechanisms to restore normal hippocampal function and thus learning and memory. Ovariectomized female rats treated with estradiol at various intervals following ovariectomy are used as a model system. Experiments involve electrophysiological measurements of NMDA currents, synaptic transmission, and long-term plasticity in acute brain slices. Determining how estradiol and hormone replacement affects hippocampal function could lead to development of therapies to alleviate hormone-dependent memory loss in aging. In a related project, we are investigating the role of estrogen in major depressive disorder to determine if estrogen replacement can alleviate depressive symptoms in menopause.

In a third project, we are investigating the role of protein O-GlcNAcylation on synaptic function and learning in rat hippocampus. Protein O-GlcNAcylation is a metabolically modulated post-translational modification whereby the monosaccharide ß-N-acetyl-glucosamine (O-GlcNAc) is attached in an o-linked fashion to serine or threonine residues of cytoplasmic or nuclear proteins. This modification is under the control of two enzymes that are highly expressed in hippocampus. O-GlcNAcylation of serine/Threonine residues is a tightly regulated process that can be thought of as analogous to phosphorylation. In Alzheimer’s disease, O-GlcNAcylation is decreased, contributing to a pathological increase in phosphorylation of Tau, which may be a contributing factor to the development of neurofibrillary tangles. In diabetes, O-GlcNAcylation is pathologically increased, which could be causal to the deficits in LTP and learning in animal models of diabetes. Thus, we are testing the hypothesis that O-GlcNAcylation of nuclear and cytoplasmic synaptic proteins is a novel, powerful regulator of acquisition and consolidation of new memories dependent upon hippocampal synaptic modification.

We employ electrophysiological recordings of neurons in acutely prepared brain slices combined with behavioral assays, pharmacology, biochemistry, morphology and immunohistochemistry to pursue our goals.

Postdoc Positions Available
Date Posted Position Title
No records
 

Selected Publications 
Publication PUBMEDID
Smith CC*, Vedder LC*, Nelson AR, Bredemann TM, and McMahon LL (2010) Duration of Estrogen Deprivation, Not Chronological Age, Prevents Estrogen’s Ability to Enhance Hippocampal Synaptic Physiology, Proc Natl Acad Sci USA Nov 9;107(45):19543-8. Epub 2010 Oct 25. PMCID: PMC2984203   
McCoy PA and McMahon LL (2010) Sympathetic sprouting in visual cortex stimulated by cholinergic denervation rescues expression of two forms of long-term depression at layer 2/3 synapses Neuroscience 14;168(3):591-604. Epub 2010 Apr 20 PMCID: PMC2892789   
McCoy PA, Norton TT, and McMahon LL (2008) Layer 2/3 synapses in the monocular and binocular regions of tree shrew visual cortex express muscarinic receptor dependent long-term depression and long-term potentiation. J. Neurophys. 100(1):336-45.   
Scheiderer CL, Smith, CC, McCutchen E, McCoy PA, Thacker EE, Dobrunz LE, McMahon LL (2008) Coactivation of M1 muscarinic and &#945;1 adrenergic receptors stimulates ERK and induces long-term depression at CA3-CA1 synapses in rat hippocampus. In Press; J. Neurosci., 2008   
McCoy PA and McMahon LL (2007) Muscarinic Receptor Dependent Long Term Depression in Rat Visual Cortex is PKC Independent but Requires ERK 1/2 Activation and Protein Synthesis J. Neurophys., 98:1862-70 2007   
McCutchen E., Scheiderer CL., Dobrunz, LE and McMahon, LL (2006) Coexistence of muscarinic long term depression with electrically induced long-term potentiation and depression at CA3-CA1 synapses. J. Neurophys. 96, 3114-21.   
Smith CC and McMahon LL (2006) Estrogen Induced Increase in the Magnitude of Long-Term Potentiation is Prevented by Blocking NR2B-Containing Receptors. J. Neurosci., 26, 8517-8522   
Scheiderer CL, McCutchen E, Thacker E, Kolasa K, Ward M, Parsons D,Harrell LE, Dobrunz LE, and McMahon LL (2006) Sympathetic Sprouting Drives Hippocampal Cholinergic Reinnervation That Prevents Loss of a Muscarinic Receptor-Induced LTD at CA3-CA1 synapses. J. Neurosci., 26, 3745-56.   
Song W, Chattipakorn SC, McMahon LL (2006) Glycine-gated chloride channels depress synaptic transmission in rat hippocampus. J. Neurophys., 95, 2366-2379.   
Smith CC, and McMahon, LL (2005) Estrogen-induced increase in the magnitude of long-term potentiation occurs only when the ratio of NMDA transmission to AMPA transmission is increased. J. Neurosci., 25:7780-7791.   
 

Keywords
hippocampus, learning, memory, acetylcholine, Alzheimer's disease, estrogen, NMDA receptors, glycine receptors

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