Mark Thomas

PhD, University of California, 1995
Area of Study: Physiology

BS, University of California, 1982
Area of Study: Physiology

Associate Professor, University of Northern Colorado
UNC School of Biological Sciences (2010 – Present)

Assistant Professor, University of Northern Colorado
UNC School of Biological Sciences (August 2006 – August 2011)

Research Assistant Professor, University of Nebraska
Medical Center (Jan 2000- July 2006)

Research Associate, University of Nebraska
Medical Center (1998-1999)

Research Associate, University of Texas
(1997-1998)

Postdoctoral Associate, University of Nebraska
Medical Center (1994 -1997)

Developmental gene expression profile in mouse Layer V prefrontal pyramidal cells

In my lab we study the physiology of Layer V pyramidal cells in the prefrontal cortex (PFC) of the mouse. The characterization of gene expression patterns in cortical neurons during development is important for a complete understanding of brain function, but is especially relevant to many psychiatric disorders which (a) have a genetic component to their etiology, and (b) involve, directly of indirectly, the PFC. This list includes schizophrenia, bipolar disorder, depression, attention deficit disorder, anxiety disorders, and autism. We are developing methods to isolate fluorescently labeled mouse PFC Layer V pyramidal neuron subtypes (the major cortical output cells) in order to extract RNA from these isolated phenotypes.. This will enable us to perform “NextGen” genetic analyses, characterizing the entire expression pattern of these neurons at different stages of postnatal development. These data should contribute to a better understanding of gene expression profiles in a subset of neurons relevant to major psychiatric disorders with a developmental component to their etiology.

Dopamine effects on electrical rhythms in mouse prefrontal pyramidal cells

Brain rhythms, such as the theta rhythm, are very important for synchronizing neuronal activity in the brain. Experiments in my lab have determined that Layer V pyramidal cells in the prefrontal cortex are electrically resonant at theta frequencies. This is very significant for their functions in the context of ongoing theta rhythmic activity in the circuits in which these cells are embedded. I have preliminary data that demonstrate that two major subtypes of dopamine receptors (D1-type and D2 type) have opposite effects on electrical resonance properties of Layer V cells. These results, which need further confirmation, would provide a unique mechanism for controlling how different parts of the brain communicate during learning and attention.

Effects of synaptic dopamine release in prefrontal brain slices using a transgenic photoactivation model.

The neurotransmitter, dopamine, exerts its effects by action potential-induced release from nerve terminals in the intact brain. Dopamine acts in two different manners: “tonic” release of dopamine regulates the levels of dopamine that occur in the brain’s extracellular fluid near dopamine-sensitive neurons, and “phasic” release, where high-frequency activation of dopamine neurons leads to activation of dopamine receptors at specific dopamine synapses on neurons. However, the mechanisms of dopamine’s actions at its several receptor subtypes are typically studied in brain slices by bath applying dopamine or its receptor agonists. This technique is entirely adequate to study the tonic effects of dopamine; however, it is inadequate to mimic the phasic effects of specific, synaptically released dopamine as occurs in the intact brain.
In this project, I will utilize transgenic mice to generate mouse brain slices where dopamine release can be elicited by applying pulses of blue light directly to the perfused brain slice. Thus, the release of dopamine from synaptic terminals can be precisely controlled by varying the frequency and duration of the light pulses, and the specific effects of dopamine released at its nerve terminals can be studied. This will open up a broad set of experiments studying mechanisms of dopamine’s actions during tonic and phasic modes of neuronal firing.
I have recently established a transgenic mouse colony here at UNC that will generate the mice needed for this project. I am very excited about the prospect of carrying out these experiments, and I believe that these experiments will allow me to make a significant, and unique contribution to the field of dopamine research.

Areas of Interest

Research in my lab focuses on the neurobiology of prefrontal brain regions and their modulation by midbrain dopamine systems. In humans, prefrontal regions are critically involved in executive functions including attention control, working memory and reward-based learning, and the selection and regulation of flexible, goal-directed behavior. We utilize a mouse model to study the cellular properties of cortical pyramidal neurons, their role in cortical networks, and their modulation by dopamine. We hope to gain insight into how these networks, when dysfunctional, may contribute to anxiety disorders (eg. PTSD), attentional disorders (eg. ADD) and other psychiatric disorders (eg. schizophrenia).

• Sheng, Z., Santiago, A.M., Thomas, M.P., Routh, V.H. (2014) Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry. Molecular and Cellular Neuroscience, 62: 30-41.
• Spindle, M.S and Thomas, M.P. (2014) Activation of 5-HT2A Receptors by TCB-2 Induces Recurrent Oscillatory Burst Discharge in Layer 5 Pyramidal Neurons of the mPFC in vitro. Physiological Reports, 2(4): 1-12.
• Reynolds, A.D., Glanzer, J.G., Kadui, I., Ricardo-Dukelow, M., Chaudhuri, A., Ciborowski, P., Cerny, R., Gelman, B., Thomas, M.P., Mosley, R.L., Gendelman, H.E. (2008) Nitrated alpha-synuclein-activated microglial profiling for Parkinson’s disease. Journal of Neurochemistry, 104(6):1504-25.
• Glanzer, J.G., Enose, Y., Wang, T., Kadiu, I, Gong, N., Rozek, W., Liu, J., Schlautman, J., Ciborowski, P.S., Thomas, M.P., Gendelman, H.E. (2007) Genomic and proteomic microglial profiling: pathways for neuroprotective inflammatory responses following nerve fragment clearance and activation. Journal of Neurochemistry,102(3): 627-645.
• M.P. Thomas, K. Chartrand, A. Reynolds, V. Vitvitsky, R. Banerjee, and H.E. Gendelman (2007) Ion channel blockade attenuates aggregated alpha synuclein induction of microglial reactive oxygen species: Relevance for the pathogenesis of Parkinson’s disease. Journal of Neurochemistry100(2): 503-519.
• V.Vitivitsky, M.P. Thomas, A. Ghorpade, H.E. Gendelman and R. Banerjee (2006) A Functional Transsulfuration Pathway in Brain Regulates Glutathione Homeostasis. Journal of Biological Chemistry281(47): 35785-35793.
• Hendricson A.W., Thomas M.P., Lippmann M.J., Morrisett R.A. (2003) Suppression of L-type voltage-gated calcium channel-dependent synaptic plasticity by ethanol: analysis of miniature synaptic currents and dendritic calcium transients. J Pharmacol Exp Ther, 307(2):550-558.
• Thomas M. P. and Morrisett, R.A. (2000) Dynamics of NMDAR-mediated neurotoxicity during chronic ethanol exposure and withdrawal. Neuropharmacology, 39: 218-226.
• Thomas M. P., Monaghan, D. T. and Morrisett R. A. (1998) Evidence for a causative role of NMDA receptors in an in vitro model of alcohol withdrawal hyperexcitability. Journal of Pharmacology & Experimental Therapeutics, 287: 87-97.
• Thomas, M.P., Webster, W.W., Norgren, R.B., Monaghan, D.T., and Morrisett, R.A. (1998) Survival and functional demonstration of interregional pathways in fore/midbrain slice explant cultures. Neuroscience,85: 615-626.
• Thomas M. P., Davis M. I., Monaghan D. T. and Morrisett R. A. (1998) Organotypic brain slice cultures for functional analysis of alcohol-related disorders: novel versus conventional preparations. Alcoholism, Clinical & Experimental Research. 22: 51-59.
• Krelstein, M.S., Thomas, M.P. and Horowitz, J.M. (1990) Thermal effects on long term potentiation in the hamster hippocampus. Brain. Res. 520, 115-122.
• Giacchino, J.L., Thomas, M.P. and Horowitz, J.M. (1988) Repetitive excitation of bursts of action potentials in the rat hippocampus following single shock excitation. Comp. Biochem. Physiol. 89A, 37-44.
• Lindley, M.A., Thomas, M.P. and Horowitz, J.M. (1987) A simulation of the effects of temperature on hippocampal neurons. Comp. Prog. in Biomed. 25, 3-12.
• Horowitz, J.M., Thomas, M. and Eckerman, P. (1987) Thermal dependence of neural activity in the hamster hippocampal slice preparation. J. Thermal Biol. 12, 97-101.
• Thomas, M.P., Martin, S.M. and Horowitz, J.M. (1986) Temperature effects on evoked potentials of hippocampal slices from noncold-acclimated, cold-acclimated and hibernating hamsters. J. Thermal Biol. 11, 213-218.