- Title: Professor
- Group: Cellular and Molecular Foundations of Intelligent Behavior
- Status: Beckman Affiliate Faculty
- Home: Pharmacology
Charles "Lee" Cox received his Ph.D. from the University of California at Riverside in 1993. He was a postdoctoral fellow at Stanford University and a research assistant professor at State University of New York, Stony Brook. He is presently an associate professor in the Department of Molecular and Integrative Physiology, head of the Department of Pharmacology in the College of Medicine and a full-time faculty member in the Beckman Institute NeuroTech group. His research interests include sensory processing, synaptic physiology and plasticity, and general properties regulating neuronal excitability. His present research focuses on the functional organization and neuromodulation of thalamocortical circuits as well as cellular mechanisms underlying epilepsy.
My fundamental interests include the understanding of cellular mechanisms underlying behavioral plasticity. Using a reductionist type approach, these cellular mechanisms likely serve as the bases for behavioral and cognitive functions such as attention, arousal, perception, learning and memory. My research is concentrated on the neurophysiology and pharmacology of neocortical and thalamic neurons in the mammalian central nervous system. The core of this research is on the cellular mechanisms involved with the regulation and modulation of neuronal excitability at both the synaptic and membrane level. These studies focus on thalamocortical circuits, because of the critical relationship of the neocortex and thalamus in sensory processing, behavioral arousal, attention and certain pathophysiological conditions such as epilepsy. While both the thalamus and neocortex are complicated structures individually, they also form an intricate, reciprocal relationship that is critical for understanding sensory/motor/associative processing at both the cellular and systems level. The importance of this works lies in the fact that the majority of behavioral activities including arousal, attention, sensory perception, learning and memory result from a concerted effort by multiple neuronal systems. Thus, information integration at the single cell level is very critical, as well as the role of these individual cells in circuit based activities. Long-lasting modifications in neuronal excitability (i.e., neuromodulation, synaptic plasticity) have also been hypothesized to be the cellular correlates underlying these behavioral activities.
The work in my lab addresses four basic issues:
- Functional organization of sensory neocortex and thalamus.
- Thalamocortical interaction and modulation.
- Brainstem regulation of thalamic/cortical neuron excitability.
- Integration of thalamocortical and intracortical information in the neocortex.
The experimental approaches we use in the laboratory include a combination of neuroanatomical, neurophysiological and neuropharmacological techniques. Our studies range from the level of single channels to intact neuronal networks in vitro. This research strategy, ranging from the study of intracellular messenger systems to the synchronized activity of large neuronal populations, should provide a better understanding of cellular mechanisms that underlie lasting modulatory changes in neuronal excitability and provide a better understanding of physiological mechanisms that underlie behavior.
We presently have ongoing collaborations with Dr. Bill Greenough involving alterations in neuronal excitability in Fragile X, and with Dr. Yuqing Li regarding cellular substrates underlying the epileptiform activity in the site specific NMDA glutamate receptor knockout animal model.
Professor Cox's sources of research funding include NIH and Phrma.
Paul, K.; Cox, C. L., Age-Dependent Actions of Dopamine on Inhibitory Synaptic Transmission in Superficial Layers of Mouse Prefrontal Cortex. Journal of Neurophysiology 2013, 109, (5), 1323-1332.
Paul, K.; Venkitaramani, D. V.; Cox, C. L., Dampened Dopamine-Mediated Neuromodulation in Prefrontal Cortex of Fragile X Mice. Journal of Physiology-London 2013, 591, (4), 1133-1143.
Crandall, S. R.; Cox, C. L., Local Dendrodendritic Inhibition Regulates Fast Synaptic Transmission in Visual Thalamus. Journal of Neuroscience 2012, 32, (7), 2513-2522.
Govindaiah, G.; Venkitaramani, D. V.; Chaki, S.; Cox, C. L., Spatially Distinct Actions of Metabotropic Glutamate Receptor Activation in Dorsal Lateral Geniculate Nucleus. Journal of Neurophysiology 2012, 107, (4), 1157-1163.
Yang, S.; Cox, C. L.; Llano, D. A.; Feng, A. S., Cell's Intrinsic Biophysical Properties Play a Role in the Systematic Decrease in Time-Locking Ability of Central Auditory Neurons. Neuroscience 2012, 208, 49-57.
Govindaiah, G.; Wang, T. F.; Gillette, M. U.; Cox, C. L., Activity-Dependent Regulation of Retinogeniculate Signaling by Metabotropic Glutamate Receptors. Journal of Neuroscience 2012, 32, (37), 12820-12831.
Wang, T. A.; Yu, Y. V.; Govindaiah, G.; Ye, X. Y.; Artinian, L.; Coleman, T. P.; Sweedler, J. V.; Cox, C. L.; Gillette, M. U., Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons. Science 2012, 337, (6096), 839-842.
Yang, S. G.; Cox, C. L., Attenuation of Inhibitory Synaptic Transmission by Glial Dysfunction in Rat Thalamus. Synapse 2011, 65, (12), 1298-1308.
Lee, S. H.; Govindaiah, G.; Cox, C. L., Selective Excitatory Actions of DNQX and CNQX in Rat Thalamic Neurons. Journal of Neurophysiology 2010, 103, (4), 1728-1734.
Paul, K.; Cox, C. L., Excitatory actions of substance P in the rat lateral posterior nucleus. European Journal of Neuroscience 2010, 31, 1-13.
Wang, D.; Govindaiah, G.; Liu, R.; De Arcangelis, V.; Cox, C. L.; Xiang, Y., Binding of Amyloid peptide to 2 adrenergic receptor induces PKA dependent AMPA receptor hyperactivity. The FASEB Journal 2010, doi: 10.1096/fj.10-156661.
Crandall, S. R.; Govindaiah, G.; Cox, C. L., Low-threshold Ca2+ current amplifies distal dendritic activity in thalamus. Journal of Neuroscience 2010, 30, 15419-15429.
Govindaiah, G.; Wang, T.; Gillette, M. U.; Crandall, S. R.; Cox, C. L., Regulation of inhibitory synapses by presynaptic D4 dopamine receptors in thalamus. Journal of Neurophysiology 2010, (104), 2757-2765.
Wang, D.; Govindaiah, G.; Liu, R.; De Arcangelis, V.; Cox, C. L.; Xiang, Y., Binding of Amyloid β peptide to β2 adrenergic receptor induces PKA dependent AMPA receptor hyperactivity. FASEB Journal 2010, 24, 3511-3521.
Paul, K.; Cox, C.L., Excitatory actions of substance P in the rat lateral posterior nucleus. European Journal of Neuroscience 2009, in press.
Govindaiah, G.; Yang, W.W.; Cox, C.L., Substance P selectively modulates GABAA receptor-mediated synaptic transmission in striatal cholinergic interneurons. Neuropharmacology 2009, in press.
Chung, L.; Moore, S.D.; Cox, C.L., Cholecystokinin action on layer 6b neurons in somatosensory cortex. Brain Research 2009, 1282, 10-19.
Beatty, J.A.; Sylwestrak, E.L.; Cox, C.L., Two distinct populations of projection neurons in the rat lateral parafascicular thalamic nucleus and their cholinergic responsiveness. Neuroscience 2009, 162, 155-173.
Govindaiah, G.; Cox, C.L., Distinct roles of metabotropic glutamate receptor activation on inhibitory signaling in the ventral lateral geniculate nucleus. Journal of Neurophysiology 2009, 101, 1761-1773.
Lee, S-H; Govindaiah, G.; Cox, C.L., Excitatory actions of peptide histidine isoleucine on thalamic relay neurons. Neuropharmacology 2008, 55, 1329-1339.
Yang, S. G.; Cox, C. L., Excitatory and anti-oscillatory actions of nitric oxide in thalamus. Journal of Physiology 2008.
Lee, S. H.; Govindaiah, G.; Cox, C.L. Heterogeneity of firing properties among rat thalamic reticular neurons. Journal of Physiology 2007, 582, 195-208.
Wilson, B. M.; Cox, C. L. Absence of metabotropic glutamate receptor-mediated plasticity in the neocortex of fragile X mice. Proceedings of the National Academy of Sciences of the United States of America 2007, 104, (7), 2454-2459.
Yang, S; Cox, C.L. Presynaptic enhancement of inhibitory activity by nitric oxide in the rat dorsal lateral geniculate nucleus. Journal of Neurophysiology 2007, 97, 3386-3395.
Yang, S. G.; Cox, C. L., Modulation of inhibitory activity by nitric oxide in the thalamus. Journal of Neurophysiology 2007, 97, (5), 3386-3395.
Govindaiah, G.; Cox, C. L. Metabotropic glutamate receptors differentially regulate GABAergic inhibition in thalamus. Journal of Neuroscience 2006, 26, (52), 13443-13453.
Govindaiah, G.; Cox, C. L. Modulation of thalamic neuron excitability by orexins. Neuropharmacology 2006, 51, (3), 414-425.
Govindaiah and Cox, C.L. (2004), "Synaptic Activation of Metabotropic Glutamate Receptors Regulates Dendritic Outputs of Thalamic Interneurons," Neuron, 41, pp. 611-623.
Lee, S.-H. and Cox, C.L. (2003), "Vasoactive Intestinal Peptide Selectively Depolarizes Thalamic Relay Neurons and Attenuates Intrathalamic Rhythmic Activity," Journal of Neurophysiology, 90, pp. 1224-1234.
Cox, C.L. and Sherman, S.M., (2000), "Control of Dendritic Outputs of Inhibitory Interneurons in the Lateral Geniculate Nucleus," Neuron, 27, pp. 597-610.
Cox, C.L., Denk, W., Tank, D., and Svoboda, K. (2000), "Action Potentials Reliably Invade Axonal Arbors of Rat Neocortical Neurons," Proceedings of the National Academy of Sciences, 97, pp. 9724-9728.
Cox, C.L. and Sherman, S.M. (1999), "Glutamate Inhibits Thalamic Reticular Neurons," Journal of Neuroscience, 19, pp. 6694-6699.
Cox, C.L., Zhou, Q., and Sherman, S.M. (1998), "Glutamate Locally Activates Dendritic Outputs of Thalamic Interneurons," Nature, 394, pp. 478-482.
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