I graduated from Cornell University in 1979 with a B.S. in Biology with a concentration in Neurobiology. From 1979-1981 I worked in the laboratory of Dr. Richard Robertson in the Department of Anatomy and Neurobiology at the University of California, Irvine. I performed my doctoral studies in the laboratory of Dr. David Prince in the Department of Neurology and Neurological Sciences at Stanford University, and received my Ph. D. in 1986. I was a Postdoctoral Fellow in the labs of Prof. Beat GÃ¤hwiler in Zurich, Switzerland, and Dr. Robert Wong, then at Columbia University. In 1990, I returned to the University of Zurich, Switzerland, as an Assistant Professor at the Brain Research Institute. I completed my Habilitation in 1993 and was promoted to Associate Professor. In January, 1998, I joined the Department of Physiology of the University of Maryland, Baltimore, School of Medicine, where I received tenure in 2002.
Synaptic plasticity: We are interested in how and when synapses change their strength during learning and memory formation (i.e. long-term potentiation and depression, or LTP and LTD). We use a combined electrophysiological and morphological approach, including focal photolysis of chemically caged glutamate to individual dendritic spines (Bagal et al., 2005). This technique has allowed us to make unique observations about the kinetics of LTP expression and to identify a change in the subunit composition of the glutamate receptors at the potentiated spine. We have also used glutamate photolysis to study the role of glutamatergic signaling in the process of synapse formation.
Experimental epilepsy: We have investigated the genesis of epilepsy as a consequence of head injury (McKinney et al., 1997; Dinocourt et al., 2011). We found that lesions lead to the massive sprouting of new axons by mature hippocampal pyramidal cells and that these new axons form an excessive number of excitatory synapses (see figure of a GFP transfected pyramidal cell axon after injury below). This axonal sprouting increases the connectivity of the hippocampus and accounts for the development of hyperexcitability in lesioned tissue. We used transgenic mice expressing mutated trkB receptors to investigate the role of neurotrophins in the initiation of axonal sprouting after injury (Dinocourt et al., 2006), with the aim of preventing the development of posttraumatic epilepsy. In addition, we have used focal release of caged glutamate to reveal that the terminal dendritic branches of the denervated CA1 cells become hyperexcitable after Schaffer collateral transection (Wei et al., 2001; Cai et al., 2004; Cai et al., 2007).
Central pain syndrome: Our observation that denervation results in changes in neuronal excitability inspired us to consider the whether this mechanism could contribute to the genesis of central pain syndromes after spinal cord injury. We have generated a rat model of this debilitating chronic pain disorder and have observed abnormal excitability in thalamic brain slices taken from these animals (Wang and Thompson, 2008). We are excited about recent findings that a specific antiepileptic drug reduces both thalamic hyperexcitability and altered pain perception in our model. We look forward to beginning a small clinical trial in the near future.
Depression: The biological basis of cognitive dysfunction in major depression remains unknown. Antidepressant medications alter monoamine concentrations, particularly serotonin, but it remains uncertain which downstream events are critical to their therapeutic effects. We have discovered that endogenous serotonin selectively potentiates some, but not all, excitatory synapses in CA1 pyramidal cells via activation of 5-HT1BRs. This potentiation is expressed postsynaptically by AMPA-type glutamate receptors and requires calmodulin-dependent protein kinase-mediated phosphorylation of GluA1 subunits. We also observed that long-term potentiation and serotonin-induced potentiation occlude each other because they share common expression mechanisms and that long-term consolidation of spatial learning is enhanced by a 5-HT1BR antagonist. Most importantly, we observed that serotonin-induced potentiation is quantitatively and qualitatively altered in the chronic unpredictable mild stress model of depression and is restored by chronic antidepressant treatment. We are currently trying to understand the mechanisms underlying these alterations and to understand how they are induced by chronic stress. The change in serotonin-mediated potentiation of synaptic excitation, and its recovery by antidepressants, implicates excitatory synapses as a locus of plasticity in depression and suggests novel targets at which to direct new antidepressant therapies.
Lab Techniques and Equipment:
- organotypic slice cultures
- whole-cell patch-clamp recording
- sharp microelectrode recording
- simultaneous recording from cell pairs
- confocal microscopy
- photolysis of caged compounds
- biolistic (gene gun) transfection
- rodent survival surgery
- Tara LeGates, PhD - Postdoctoral Fellow
- Mark Kvarta, MD/PhD student - stress and depression
- Adam Van Dyke, PhD student - serotonin receptor second messenger signaling and depression
Kallarackal A.J., Kvarta, M.D., Camaratta, E., Jaberi, L., Cai, X., Bailey, A.M. and Thompson, S.M. (2013) Chronic stress induces a selective decrease in AMPA receptor-mediated synaptic excitation at hippocampal temporoammonic-CA1 synapses. J. Neurosci., 33: 15669 –15674.
Aungst, S., England, P.M. and Thompson, S.M. (2013) Critical role of trkB receptors in reactive axonal sprouting and hyperexcitability after axonal injury. J. Neurophysiol., 109: 813-824. (Editor’s Choice selection). PMCID: PMC3567381
Cai, X., Kallarackal, A.J., Kvarta, M. D., Goluskin, S., Gaylor, K., Bailey, A.M., Lee, H.-K., Huganir, R.L. and Thompson, S.M. (2013) Local potentiation of excitatory synapses by serotonin and antidepressants and its dysregulation in rodent models of depression. Nature Neurosci., 16: 464–472. PMCID: PMC3609911
Wang, G., and Thompson S.M. (2008) Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: Thalamic hyperexcitability after spinothalamic tract lesions. Journal of Neuroscience, 28: 11959 –11969. PMCID: PMC2627563
Cai X., Wei D.-S., Gallagher S.E., Bagal A., Mei Y.-A., Kao J. P. Y., Thompson S. M., and Tang C.-M. (2007) Hyperexcitability of distal dendrites in hippocampal pyramidal cells following chronic partial deafferentation. Journal of Neuroscience 27: 59-68.
Dinocourt, C., Gallagher S.E., and Thompson S.M. (2006) Injury-induced axonal sprouting in the hippocampus is initiated by activation of trkB receptors. European Journal of Neuroscience 24: 1857-1866.
Bagal A., Kao J. P. Y., Tang C.-M., and Thompson S.M. (2005) Long-term potentiation of exogenous glutamate responses at single dendritic spines. Proceedings of the National Academy of Science USA 102: 14434-14439.
Cai X., Liang C.W., Muralidharan S., Kao J.P.Y., Tang C-M, and Thompson S.M. (2004) Unique roles of SK and Kv4.2 potassium channels in dendritic integration. Neuron 44: 351-364, 2004.
Wei D.-S., Mei Y.-A., Bagal A., Kao J.P.Y., Thompson S.M., and Tang C.-M. (2001) Compartmentalized and binary behavior of terminal apical dendrites in hippocampal pyramidal neurons. Science 293: 2271-2275.
McKinney R.A., Debanne D., Gahwiler B.H., and Thompson S.M. (1997) Lesion-induced axonal sprouting and hyperexcitability in the hippocampus in vitro: implications for the genesis of posttraumatic epilepsy. Nature Medicine 3: 990-996.
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