Email:  mcmahon@uab.edu
  Telephone: 205.934.3523
  Fax: 205.975.9028
  Bldg/Room: MCLM 964

Research

Inadequate functioning of inhibitory GABAergic neurons in the central nervous system leads to pathological conditions such as epilepsy and excitotoxic cell death. My laboratory is interested in understanding the role of inhibitory interneurons and inhibitory mechanisms in governing the activity of local synaptic circuits. A major effort is aimed at understanding the role of the inhibitory amino acids, glycine and taurine, and glycine-gated chloride channels in providing neuronal inhibition in hippocampus, a brain region highly susceptible to seizure activity and excitotoxic cell death. Our experiments are directed at determining whether enhancing glycine channel activity with receptor agonists and modulators depress seizure activity and prevent or minimize excitotoxic cell death.

Another major focus of the laboratory is directed toward elucidating the cellular and molecular mechanisms that underlie long-term changes in the strength of excitatory synaptic transmission and how these mechanisms are altered in neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease. Presently, we are examining a novel form of long-term depression (LTD) in hippocampus that is induced via activation of the M1 subtype of muscarinic cholinergic receptors. In this study, we are testing the hypothesis that expression of this plasticity requires intact cholinergic innervation of hippocampus and is necessary for normal learning and memory. The potential loss of this plasticity in aged animals and animal models of Alzheimer’s Disease could contribute to cognitive decline. 

Finally, we are examining the effects of estrogen on synaptic function and plasticity. We are interested in determining how estrogen-induced changes in synaptic plasticity contribute to the memory enhancing effects of this hormone.

We employ electrophysiological recordings of neurons in acutely prepared brain slices and in dissociated neuronal cultures combined with pharmacological, molecular, morphological and immunohistochemical techniques to pursue our goal.

Selected Publications

1. Howlett AC, Champion-Dorrow TM, McMahon LL, Westlake TM. (1991) The cannabinoid  receptor: biochemical and cellular properties in neuroblastoma cells.  Pharm. Biochem. and Behav. 40: 565-569.
    

2. Chiappinelli VA, Wolf KM, Feng C, Yum L, McMahon LL. (1993) Different responses to opioids measured in terminals and somas of Edinger-Westphal neurons. Neurosci. 57:425-432.
    

3. McMahon LL, Yoon K.-W., Chiappinelli VA. (1994) Electrophysiological evidence for presynaptic nicotinic receptors in the avian ventral lateral geniculate nucleus. J. Neurophys. 71:826-829.
    

4. McMahon LL, Yoon K.-W., Chiappinelli VA. (1994) Nicotinic receptor activation facilitates GABAergic neurotransmission in the avian lateral spiriform nucleus. Neurosci. 59:689-698.
    

5. McMahon LL, Kauer JA. (1997) Hippocampal interneurons express a novel form of synaptic plasticity. Neuron, 18:295-305.
    

6. McMahon LL, Kauer JA. (1997) Hippocampal interneurons are excited by serotonin-gated ion channels. J. Neurophys., 78:2493-2502.
    

7. McMahon LL, Williams JH, Kauer JA. (1998) Functionally distinct groups of interneurons identified during rhythmic oscillations in hippocampus. J. Neurosci. 18:5640-5651.
    

8. Chattipakorn SC, McMahon LL. (2002) Pharmacological characterization of glycine-gated chloride       currents recorded in rat hippocampal slices. J. Neurophys. 87:1515-1525.
    

9. Chattipakorn SC, McMahon LL (2003) Strychnine-sensitive glycine receptors depress hyperexcitability in rat dentate gyrus. J. Neurophys. J. Neurophys. 89:1339-1342.
    

10. Jovov, B., A. Tousson, McMahon LL, and D.J. Benos. (2003) Immunolocalization of the acid-sensing ion channel 2a in the rat cerebellum. Histochem. Cell Biol., 119:437-446.
     

11. Scheiderer CL, Dobrunz LE, McMahon LL. (2004) A novel form of long-term synaptic depression in rat hippocampus induced by activation of a adrenergic receptors. J. Neurophys. 91:1071-1077.
     

12. Shaughnessy L, Chamblin B, McMahon L, Nair A, Thomas MB, Wakefield J, Koentgen F, Ramabhadran R. (2004) Novel approaches to models of Alzheimer’s disease pathology fro drug screening and development. J Mol Neurosci 24:23-32.
     

13. 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.
     

14. Song W, Chattipakorn SC, McMahon LL (2006) Glycine-gated chloride channels depress synaptic transmission in rat hippocampus. J. Neurophys., 95, 2366-2379.
     

15. 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.
     

16. 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.
     

17. 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.
     

18. McCoy PA and McMahon LL (2007) Muscarinic Receptor Dependent Long Term Depression in Rat  Visual Cortex is NMDAR Independent and Requires ERK 1/2 Activation. In Press, J. Neurophys, June 2007).
     

19.  McCoy PA, Norton TT, and McMahon LL (2007) Muscarinic Receptor Dependent Plasticity at Synapses in Layer 2/3 of Tree Shrew Visual Cortex Utilize Different Signaling Mechanisms in Binocular vs. Monocular Regions. (submitted, Journal of Neuroscience).