Thomas P. Sutula

 

 

Hippocampal Plasticity in Development, Memory, and Epilepsy

E-mail: sutula@neurology.wisc.edu

Research Strengths: Development: Plasticity and Repair, Neurobiology of Disease

The laboratory studies activity-dependent circuit plasticity in the developing and adult hippocampus, a region of brain that plays a role in learning, memory, and epilepsy. Previous studies from the laboratory have demonstrated that seizures (an intense form of neural activity) induce enhanced synaptic transmission, progressive neuronal death, and axon sprouting which are accompanied by permanent functional alterations in hippocampal circuits including increased susceptibility to additional seizures and memory dysfunction. In developing rats, seizures also modify formation of hippocampal circuits and induce long-term alterations in the capacity for hippocampal synaptic plasticity and learning. Acute and chronic electrophysiological, anatomical, and behavioral methods are being used to study how neural activity and seizures modify the hippocampal organization and function. A variety of molecular and genomic approaches are being used to study how long-term alterations in hippocampal circuits are produced by neural activity, and we are also examining how alterations in the extracellular ionic environment interacting with seizure-induced circuit reorganization in the dentate gyrus contribute to emergent properties such as recurrent excitation and network synchronization.

Lab Website:

http://www.neurology.wisc.edu/sutula.html

Selected Publications:

• Sutula, T.P., and F.E. Dudek. 2007. Unmasking recurrent excitation generated by mossy fiber sprouting in the epileptic dentate gyrus: an emergent property of a complex system. Prog Brain Res. 163: 543-566
• Garriga-Canut, M., B. Schoenike, R. Qazi, K. Bergendahl, T.J. Daley, R. Pfender, J.F. Morrison, J. Ockuly, C. Stafstrom, T. Sutula, and A. Roopra. 2006. 2-deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP - dependent metabolic regulation of chromatin structure. Nature Neuroscience 9:1382-1387 [PDF]
• Westmark, C., V. Bartleson, F. Gourronc, U. Sayin, S. Bhattacharya, T. Sutula, and J. Malter. 2005. HuR Interacts with a large number of mRNA ligands in mouse hippocampus after seizure. Journal of Experimental Neurology and Neuropathology 64:1037-1045
• Sayin, U., T. Sutula, and C. Stafstrom. 2004. Seizures in the developing brain cause adverse long-term effects on spatial learning and anxiety. Epilepsia 45: 1539-1548 [PDF]
• Sayin Ü., S. Osting, J. Hagen, P. Rutecki, and T. Sutula. 2003. Spontaneous seizures and loss of axo-axonic and axo-somatic inhibition induced by repeated brief seizures in kindled rats. J. Neurosci. 23: 2759-2768. [PDF]
• Cavazos, J., P. Zhang, R. Qazi, and T. Sutula. 2003. Ultrastructural features of sprouted mossy fiber synapses in kindled and kainic acid treated rats. J. Comp. Neurol. 458: 272-292.
• Kotloski, R., M. Lynch, S. Lauersdorf, and T. Sutula. 2002. Repeated brief seizures induce progressive hippocampal neuron loss and memory deficits. Prog. Brain Res. 135: 95-110.
• Pitkanen, A. and T. Sutula. 2002. Is epilepsy a progressive disorder?- Prospects for new therapeutic approaches in temporal lobe epilepsy. Lancet Neur. 1: 173-181. [PDF]
• Lynch, M. and T. Sutula. 2000. Recurrent excitatory connectivity in the dentate gyrus of kindled and kainic acid-treated rats. J. Neurophysiol. 83: 693-704. [PDF]
• Lynch, M., Ü. Sayin, P. Rutecki, and T. Sutula. 2000. Long-term consequences of early postnatal seizures on hippocampal learning and plasticity. Eur. J. Neurosci. 12: 2252-2264.
• Lynch, M., Ü Sayin, G. Golarai, and T. Sutula. 2000. NMDA receptor-dependent plasticity of granule cell spiking in the dentate gyrus of normal and epileptic rats. J. Neurophysiol. 84: 2868-2879. [PDF]
• Sayin, Ü, P. Rutecki, and T. Sutula. 1999. NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling. J. Neurophysiol. 81: 564-574. [PDF]
• Sutula, T., P. Zhang, Lynch, M., Ü Sayin, G. Golarai, and R. Rod. 1998. Synaptic and axonal remodeling of mossy fibers in the hilus and supragranular region of the dentate gyrus in kainate-treated rats. J. Comp. Neurol. 390: 578-594. [PDF]