My lab is interested in the circuit and cellular changes associated with the development of the chronic state in humans and in animal models of temporal lobe epilepsy. We use a variety of electrophysiological and anatomical techniques including whole cell patch clamp in brain slices and cell fills to examine these issues.
While many animal models of epilepsy have been developed, it is important to have a thorough understanding of the human pathology so that the models can be evaluated. We have the opportunity to examine human material resected for the treatment of medically intractable seizures and found that in there are numerous changes in the network properties in one part of the hippocampus, the dentate gyrus. We have primarily focused on alterations in the inhibitory system and have described several changes in both the inhibitory circuitry as well as in the regulation of the availability of GABA, the primary inhibitory transmitter in the central nervous system. Many of these changes also occur in an animal model of temporal lobe epilepsy, the kainate-treated rat, and we are currently studying them in greater detail.
As part of this effort, we are examining synaptic plasticity in the human material with an eye to examining the link between alterations in synaptic function and brain function.
Overexpression of GluR6 in rat hippocampus produces seizures and spontaneous non-synaptic bursting in vitro.
Telfeian, A.E., Federoff, H, Leone, P, During, M.J. and Williamson, A. 2000. Overexpression of GluR6 in rat hippocampus produces seizures and spontaneous non-synaptic bursting in vitro. Neurobiol. of Disease. 7:362-374.
NPY inhibits glutamateric excitation in the epileptic human hippocampus.
Patrylo, P.R., Spencer, D.D, van den Pol, A., and Williamson, A. 1999. NPY inhibits glutamateric excitation in the epileptic human hippocampus. J Neurophysiol 82:478-83.
- Regulation of excitability in the epileptic human hippocampus. Williamson, A. and Patrylo, P. Regulation of excitability in the epileptic human hippocampus. 1999. The Neuroscientist 5:362-370.